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0 | PMC2565068-02-Results-07 | [
{
"id": "PMC2565068-02-Results-07__text",
"type": "abstract",
"text": [
"scpC and slo are insufficient singly for the pathogenesis of invasive infections \nFinally, we assessed the influence of enhanced expression of the scpC or the slo gene on the virulence in a mouse model. As shown in Table 1, NIH230scpC and NIH230slo exerted the LD50 value 3-10 fold lower than that of the non-invasive isolate 1566, but 10-30 fold higher than that of severe invasive isolates. Subcutaneous inoculation of NIH230scpC and NIH230slo yielded the local infected lesions with area comparable to those of 1566 and NIH230::csrS+ during the course of infection (Figure 7D). These results suggest that enhanced expression of ScpC and SLO in invasive GAS plays an important role in vivo virulence of GAS infection.\n"
],
"offsets": [
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}
] | [
{
"id": "PMC2565068-02-Results-07_T1",
"type": "Protein",
"text": [
"scpC"
],
"offsets": [
[
0,
4
]
],
"normalized": []
},
{
"id": "PMC2565068-02-Results-07_T2",
"type": "Protein",
"text": [
"slo"
],
"offsets": [
[
9,
12
]
],
"normalized": []
},
{
"id": "PMC2565068-02-Results-07_T3",
"type": "Protein",
"text": [
"scpC"
],
"offsets": [
[
147,
151
]
],
"normalized": []
},
{
"id": "PMC2565068-02-Results-07_T4",
"type": "Protein",
"text": [
"slo"
],
"offsets": [
[
159,
162
]
],
"normalized": []
},
{
"id": "PMC2565068-02-Results-07_T5",
"type": "Organism",
"text": [
"mouse"
],
"offsets": [
[
190,
195
]
],
"normalized": []
},
{
"id": "PMC2565068-02-Results-07_T6",
"type": "Organism",
"text": [
"NIH230scpC"
],
"offsets": [
[
224,
234
]
],
"normalized": []
},
{
"id": "PMC2565068-02-Results-07_T7",
"type": "Protein",
"text": [
"scpC"
],
"offsets": [
[
230,
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]
],
"normalized": []
},
{
"id": "PMC2565068-02-Results-07_T8",
"type": "Organism",
"text": [
"NIH230slo"
],
"offsets": [
[
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]
],
"normalized": []
},
{
"id": "PMC2565068-02-Results-07_T9",
"type": "Protein",
"text": [
"slo"
],
"offsets": [
[
245,
248
]
],
"normalized": []
},
{
"id": "PMC2565068-02-Results-07_T10",
"type": "Organism",
"text": [
"non-invasive isolate 1566"
],
"offsets": [
[
305,
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]
],
"normalized": []
},
{
"id": "PMC2565068-02-Results-07_T11",
"type": "Organism",
"text": [
"NIH230scpC"
],
"offsets": [
[
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]
],
"normalized": []
},
{
"id": "PMC2565068-02-Results-07_T12",
"type": "Protein",
"text": [
"scpC"
],
"offsets": [
[
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]
],
"normalized": []
},
{
"id": "PMC2565068-02-Results-07_T13",
"type": "Organism",
"text": [
"NIH230slo"
],
"offsets": [
[
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"normalized": []
},
{
"id": "PMC2565068-02-Results-07_T14",
"type": "Protein",
"text": [
"slo"
],
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[
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],
"normalized": []
},
{
"id": "PMC2565068-02-Results-07_T15",
"type": "Organism",
"text": [
"1566"
],
"offsets": [
[
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],
"normalized": []
},
{
"id": "PMC2565068-02-Results-07_T16",
"type": "Organism",
"text": [
"NIH230::csrS+"
],
"offsets": [
[
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]
],
"normalized": []
},
{
"id": "PMC2565068-02-Results-07_T17",
"type": "Protein",
"text": [
"csrS+"
],
"offsets": [
[
531,
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]
],
"normalized": []
},
{
"id": "PMC2565068-02-Results-07_T18",
"type": "Protein",
"text": [
"ScpC"
],
"offsets": [
[
631,
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]
],
"normalized": []
},
{
"id": "PMC2565068-02-Results-07_T19",
"type": "Protein",
"text": [
"SLO"
],
"offsets": [
[
640,
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]
],
"normalized": []
},
{
"id": "PMC2565068-02-Results-07_T20",
"type": "Organism",
"text": [
"invasive GAS"
],
"offsets": [
[
647,
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]
],
"normalized": []
},
{
"id": "PMC2565068-02-Results-07_T21",
"type": "Organism",
"text": [
"GAS"
],
"offsets": [
[
705,
708
]
],
"normalized": []
}
] | [
{
"id": "PMC2565068-02-Results-07_E1",
"type": "Process",
"trigger": {
"text": [
"infections"
],
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70,
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]
]
},
"arguments": []
},
{
"id": "PMC2565068-02-Results-07_E2",
"type": "Regulation",
"trigger": {
"text": [
"influence"
],
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]
},
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"ref_id": "PMC2565068-02-Results-07_E8"
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{
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"ref_id": "PMC2565068-02-Results-07_E4"
}
]
},
{
"id": "PMC2565068-02-Results-07_E3",
"type": "Regulation",
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"text": [
"influence"
],
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]
]
},
"arguments": [
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"role": "Theme",
"ref_id": "PMC2565068-02-Results-07_E8"
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}
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"enhanced"
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"ref_id": "PMC2565068-02-Results-07_E6"
}
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"type": "Positive_regulation",
"trigger": {
"text": [
"enhanced"
],
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},
"arguments": [
{
"role": "Theme",
"ref_id": "PMC2565068-02-Results-07_E7"
}
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{
"id": "PMC2565068-02-Results-07_E6",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
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"arguments": [
{
"role": "Theme",
"ref_id": "PMC2565068-02-Results-07_T3"
}
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"id": "PMC2565068-02-Results-07_E7",
"type": "Gene_expression",
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"text": [
"expression"
],
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]
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"role": "Theme",
"ref_id": "PMC2565068-02-Results-07_T4"
}
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"id": "PMC2565068-02-Results-07_E8",
"type": "Process",
"trigger": {
"text": [
"virulence"
],
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]
]
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"arguments": []
},
{
"id": "PMC2565068-02-Results-07_E9",
"type": "Process",
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"text": [
"infected"
],
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},
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"role": "Participant",
"ref_id": "PMC2565068-02-Results-07_T13"
}
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"text": [
"infected"
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"role": "Participant",
"ref_id": "PMC2565068-02-Results-07_T15"
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"infected"
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"role": "Participant",
"ref_id": "PMC2565068-02-Results-07_T16"
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"infected"
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"infection"
],
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"enhanced"
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"enhanced"
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"ref_id": "PMC2565068-02-Results-07_E17"
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"expression"
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"role": "Theme",
"ref_id": "PMC2565068-02-Results-07_T18"
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"expression"
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"ref_id": "PMC2565068-02-Results-07_T19"
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"important role"
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"important role"
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"virulence"
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}
] | [] | [] |
1 | PMC2816692-03-Discussion-02 | [
{
"id": "PMC2816692-03-Discussion-02__text",
"type": "abstract",
"text": [
"Implications for type III secretion function \nThe interaction between SrcA and SsaN supports an emerging paradigm whereby secretion chaperones bring effector cargo to the T3SS through physical interaction with the hexameric ATPase at the base of the apparatus [14]. This was demonstrated for chaperone-ATPase components in the flagellar type III system [17] and in non-flagellar type III systems in E. coli [27] and the SPI-1 system in Salmonella [15]. Our work shows the first chaperone-ATPase interaction for a T3SS functioning from within an intracellular vacuolar compartment and supports this interaction as a more generalize feature of type III secretion function. In our experiments, we could induce the ATPase domain of SsaN to oligomerize in the presence of SrcA, but not in its absence, which was intriguing because the purified enzyme lacked a domain at the carboxyl terminus thought to be involved in oligomer stability, at least for E. coli EscN [14]. These data suggest that type III chaperones might have an as yet undefined role in assembly of the ATPase homohexamer that gives rise to efficient effector translocation. This will be an important area for further experimentation in this and other systems.\n"
],
"offsets": [
[
0,
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] | [
{
"id": "PMC2816692-03-Discussion-02_T1",
"type": "Protein",
"text": [
"SrcA"
],
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[
70,
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]
],
"normalized": []
},
{
"id": "PMC2816692-03-Discussion-02_T2",
"type": "Protein",
"text": [
"SsaN"
],
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[
79,
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]
],
"normalized": []
},
{
"id": "PMC2816692-03-Discussion-02_T3",
"type": "Organism",
"text": [
"E. coli"
],
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[
399,
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]
],
"normalized": []
},
{
"id": "PMC2816692-03-Discussion-02_T4",
"type": "Organism",
"text": [
"Salmonella"
],
"offsets": [
[
436,
446
]
],
"normalized": []
},
{
"id": "PMC2816692-03-Discussion-02_T5",
"type": "Protein",
"text": [
"SsaN"
],
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[
728,
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]
],
"normalized": []
},
{
"id": "PMC2816692-03-Discussion-02_T6",
"type": "Protein",
"text": [
"SrcA"
],
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[
767,
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]
],
"normalized": []
},
{
"id": "PMC2816692-03-Discussion-02_T7",
"type": "Chemical",
"text": [
"carboxyl"
],
"offsets": [
[
869,
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]
],
"normalized": []
},
{
"id": "PMC2816692-03-Discussion-02_T8",
"type": "Organism",
"text": [
"E. coli"
],
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[
946,
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]
],
"normalized": []
},
{
"id": "PMC2816692-03-Discussion-02_T9",
"type": "Protein",
"text": [
"EscN"
],
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[
954,
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]
],
"normalized": []
},
{
"id": "PMC2816692-03-Discussion-02_T12",
"type": "Entity",
"text": [
"ATPase domain"
],
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[
711,
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]
],
"normalized": []
}
] | [
{
"id": "PMC2816692-03-Discussion-02_E1",
"type": "Binding",
"trigger": {
"text": [
"interaction"
],
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[
50,
61
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMC2816692-03-Discussion-02_T1"
},
{
"role": "Theme",
"ref_id": "PMC2816692-03-Discussion-02_T2"
}
]
},
{
"id": "PMC2816692-03-Discussion-02_E2",
"type": "Positive_regulation",
"trigger": {
"text": [
"induce"
],
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[
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMC2816692-03-Discussion-02_E3"
}
]
},
{
"id": "PMC2816692-03-Discussion-02_E3",
"type": "Binding",
"trigger": {
"text": [
"oligomerize"
],
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[
736,
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMC2816692-03-Discussion-02_T5"
},
{
"role": "Site",
"ref_id": "PMC2816692-03-Discussion-02_T12"
}
]
}
] | [] | [] |
2 | PMC2858072-02-Results_and_Discussion-02 | [
{
"id": "PMC2858072-02-Results_and_Discussion-02__text",
"type": "abstract",
"text": [
"Regulation of carbon and nitrogen metabolism \nOne of the remarkable findings observed in our microarray analysis was that several genes related with metabolism were also differentially expressed. These included twelve genes encoding ABC transport systems (matE, BAB1_0340; dctM, BAB1_0372; fhuD, BAB1_1366; yadH, BAB1_1368; oppA, BAB1_1601; oppC, BAB2_1051; oppD, BAB2_0817; potC, BAB1_ 1624; ssuB, BAB2_0917; ugpC, BAB2_1143; BAB2_0794; BAB2_1139), ten genes related with carbohydrate, amino or fatty acids metabolism and five related with nitrogen metabolism. Interestingly, all genes related with carbohydrate, amino or fatty acids metabolism were up-regulated in the bvrR mutant. These included the first enzyme in gluconeogenesis (pckA, phosphoenolpyruvate carboxykinase, BAB1_2091), four genes involved in TCA cycle and pyruvate metabolism (fumB, fumarate hydratase, BAB1_0977; lpdA, dihydrolipoamide dehydrogenase, BAB2_0712; pyruvate dehydrogenase, BAB2_0032; acetyl-CoA acetyltransferase, BAB2_0443), three genes involved in amino or fatty acid metabolism (aldehyde dehydrogenases, BAB2_1130, BAB2_1114; hydroxymethylglutaryl-CoA lyase, BAB1_0017), and two genes involve in benzoate degradation (pcaC, carboxymuconolactone decarboxylase, BAB2_0597; pcaI, coenzyme A transferase, BAB2_0604). In addition, the complete maltose transport system of Brucella, which consists in a large operon containing thirteen genes (BAB1_0236-0248) was also affected. Ten of these genes, including malK, malG, malF, malE and an iclR regulator, were down-regulated suggesting that the complete operon was negatively regulated in the bvrR mutant. Although it has been showed that the mutants in the BvrR/BvrS system have no obvious defects with regard to the ability to grow on standard media [4], our microarray results suggests that the BvrR/BvrS system controls elements directly involved in adjusting the Brucella metabolism to the nutrient shift expected to occur during the transit to the intracellular niche. To determine if the BvrR/BvrS system affects the metabolism, bvrR mutant and wild type strains were grown in synthetic minimal media. As show in Figure 3, growth of the bvrR mutant was significantly reduced in minimal media. Other genes differentially expressed in the bvrR mutant included denitrification genes. The nitrite reductase gene ( nirK, BAB2_0943) was down regulated and the nitric oxide and nitrous oxide reductases genes ( nor C, BAB2_0955; nosZ, BAB2_0928) were up regulated. On the other hand, two deaminases (glutaminase, BAB2_0863; guanine deaminase, BAB1_0383) were also affected. Since Brucella is an intracellular facultative pathogen, the bacteria could use these denitrification reactions to grow under low-oxygen condition by respiration of nitrate. Brucella may also take advantage of denitrification to cope with nitric oxide (NO) production in the macrophage during the innate response against infection. In fact, some of these denitrification genes have been related with the virulence in mice [10], [11]. Interestingly, our experiments to study the intracellular transcriptional level of BvrR/BvrS controlled genes (see below) showed that whereas norC was induced intracellularly, nirK and nosZ were less expressed. Taken together all these data support the proposal that one role of the BvrR/BvrS system could be neutralize the production of toxic reactive nitrogen molecules, as NO, by the host. These results also demonstrated a connection between carbon and nitrogen metabolism and BvrR/BvrS in Brucella. Our results also demonstrated that gene hpr-K (BAB1_2094), a member of the Brucella phosphotransferase system (PTS; BAB1_2097-2094) adjacent to the bvrR/bvrS, was down-regulated. As mentioned before, phosphoenolpyruvate carboxykinase gene (pckA, BAB1_2091) which is located upstream of the regulatory gene bvrR and divergently expressed was up-regulated. Comparative genome analysis revealed that in addition to the bvrR/bvrS genes, the genome structure around these genes is essentially the same for all the alpha-proteobacteria [5]. Genes encoding proteins related to the PTS, including a HPr Ser-kinase, an EIIA permease of the mannose family and a HPr homologue precede those of the two-component regulatory system. In most of these loci, upstream of the regulatory gene the pckA is divergently expressed (Figure 2). This gene catalyzes the reversible decarboxylation and phosphorylation of oxaloacetate to form phosphoenolpyruvate. In alpha-proteobacteria, it has been proposed that HPr might control the phosphorylation state of the transcription regulator [12]-[14]. In this regard, Letesson and col. [15] have suggested that in Brucella the PTS could interact with the BvrS sensor kinase, which in turn phosphorylates the response regulator. Then, the BvrR could control transcription of the pckA gene, which encodes an essential control enzyme of the gluconeogenesis and Krebs cycle. This hypothesis could explain the observation that mutants in the regulatory gene bvrR were inhibited in minimal media (see above). According to this, it has been demonstrated that in A. tumefaciens the pckA genes is indeed under the control of ChvG/ChvI [16] and that null mutants in S. meliloti exoS and chvI have pleiotropic growth defects and were unable to grow on several carbon sources [17]. A link between carbon and nitrogen metabolism, PTS and two-component regulatory systems have been proposed for some bacteria [18], and our microarray results strongly suggest that same relationship could be made for Brucella.\n"
],
"offsets": [
[
0,
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}
] | [
{
"id": "PMC2858072-02-Results_and_Discussion-02_T1",
"type": "Chemical",
"text": [
"carbon"
],
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[
14,
20
]
],
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},
{
"id": "PMC2858072-02-Results_and_Discussion-02_T2",
"type": "Chemical",
"text": [
"nitrogen"
],
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[
25,
33
]
],
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},
{
"id": "PMC2858072-02-Results_and_Discussion-02_T3",
"type": "Protein",
"text": [
"matE"
],
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[
256,
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],
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3 | PMC2639726-02-Results-04 | [
{
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"text": [
"Validation of SPI-2 regulation \nSPI-2 encodes a type III secretion system and secreted effectors required for systemic mouse infection [8],[9]. To assess the effects of growth conditions on expression of the SPI-2 secretion apparatus we constructed a lacZ transcriptional fusion to ssaG, a component of the secretion apparatus, and tested expression in each mutant background under each of the four growth conditions. At the same time we determined transcript levels via quantitative real-time PCR (qRT-PCR), using transcripts from rpoD and gyrB as controls [51]. We observed that the results determined by these two methods matched closely (Figure S2) and that the level of transcription of ssaG was highest when Salmonella was grown in minimal acidic media. In agreement with the microarrays, the effect of these regulators on ssaG expression was minimal if the bacteria were grown in rich media (LB broth). Because the type III secretion system and associated virulence factors encoded within SPI-2 were most highly expressed in acidic minimal media we therefore focused on growth in this media and used qRT-PCR to measure transcript levels. To validate the transcriptional profiles we prepared RNA from mutants and parent bacteria grown in acidic minimal medium and used as template for qRT-PCR. Six promoters have been identified for the type III secretion system encoded within SPI-2 (see Figure 4; [52]). We monitored transcription of seven genes within SPI-2, covering each operon at least once, and used gyrB transcript as an internal control. We observed a decrease in transcription of all 7 genes in 11 of the 14 mutants. The three exceptions were spvR, fruR, and rpoS. Strains containing mutations in phoP/phoQ, ssrA/ssrB, slyA, and ompR/envZ showed at least 100-fold decreases in transcription of all SPI-2 genes (Figure 4). Mutations of ihf (himD) and csrA showed an intermediate level of 8-16-fold decreased transcription whereas hnr, rpoE, smpB, crp and hfq showed a modest decrease of 2-8-fold. The results of this analysis are generally concordant with the microarray results although the dynamic range was larger for qRT-PCR than for the microarrays as has been observed before [53]. Note that rpoE and hfq mutants showed a dramatic reduction in macrophage survival, but little difference in transcription of SPI-2 genes during growth in AMM. It has recently been reported that the translational regulator Hfq, regulates translation of RpoE explaining in part why the two mutations behave similarly [54]. Furthermore, Hfq regulates translation of more than 20% of all Salmonella proteins explaining why a mutation in this gene has such a dramatic phenotype ([54]; Charles Ansong, Hyunjin Yoon, Steffen Porwollik, Heather Mottaz-Brewer, Briana Ogata-Petritis, Navdeep Jaitly, Joshua N. Adkins, Michael McClelland, Fred Heffron, and Richard D. Smith; Global systems-level analysis of small RNA-mediated translational regulation: Implications for virulence and global protein translation; Submitted).\n"
],
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"expression"
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"effect"
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}
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"text": [
"decrease"
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1990,
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]
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}
]
},
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"id": "PMC2639726-02-Results-04_E20",
"type": "Negative_regulation",
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"text": [
"decrease"
],
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[
1990,
1998
]
]
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{
"role": "Theme",
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}
]
},
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"id": "PMC2639726-02-Results-04_E21",
"type": "Negative_regulation",
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"text": [
"decrease"
],
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[
1990,
1998
]
]
},
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"role": "Theme",
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}
]
},
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"id": "PMC2639726-02-Results-04_E22",
"type": "Negative_regulation",
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"text": [
"decrease"
],
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[
1990,
1998
]
]
},
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"type": "Negative_regulation",
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"text": [
"decrease"
],
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1990,
1998
]
]
},
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{
"role": "Theme",
"ref_id": "PMC2639726-02-Results-04_E17"
}
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"regulates"
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"role": "Theme",
"ref_id": "PMC2639726-02-Results-04_T36"
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}
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"virulence"
],
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2963,
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]
},
"arguments": []
}
] | [
{
"id": "PMC2639726-02-Results-04_1",
"entity_ids": [
"PMC2639726-02-Results-04_T23",
"PMC2639726-02-Results-04_T24"
]
}
] | [] |
4 | PMC2816692-02-Results-05 | [
{
"id": "PMC2816692-02-Results-05__text",
"type": "abstract",
"text": [
"SrcA binds effector cargo destined for the SPI-2 T3SS \nSince structural and biochemical data unambiguously defined SrcA as a T3SS-associated chaperone, we used two experimental approaches to identify SrcA cargo(s). First, we used stable isotope labeling of amino acids in cell culture (SILAC) [28] in conjunction with quantitative mass spectrometry-based proteomics to identify cargo immunoprecipitated with SrcA from Salmonella. For this series of experiments we constructed a mutant in which the srcA gene was replaced on the chromosome with srcA-FLAG to enable immunoprecipitation from cell lysates. Lysates prepared from wild type cells grown in 2H4-Lys and 13C6-Arg containing SILAC medium (heavy) and srcA mutant cells grown in medium containing natural amino acids of Lys and Arg (light) were mixed and subjected to an immunoprecipitation procedure with an anti-FLAG antibody followed by quantitative mass spectrometry. Peptides originating from wild type cells contained heavy atom-substituted lysine and arginine such that putative SrcA cargo proteins would generate low heavy:light SILAC peptide ratios from the complex mixtures (Fig. 5A). In these experiments the T3SS effector protein SseL was identified by quantitative SILAC mass spectrometry as a specific SrcA cargo protein (Fig. 5B). SseL was immunoprecipitated specifically along with SrcA-FLAG with a SILAC ratio of 0.08, whereas additional abundant proteins displayed SILAC ratios closer to approximately1 (OmpF is shown, Fig. 5B) (mean SILAC ratio of all other peptides identified was 0.93 (Dataset S1). Secondly, to verify the mass spectrometry data and to identify other possible effector cargo, we examined the secretion profiles of wild type cells and an srcA mutant that each expressed HA-tagged effector genes, the products of which are secreted by the SPI-2-encoded T3SS. Using this approach SseL-HA and PipB2-HA were depleted from the secreted protein fraction of srcA mutant cells (Fig. 5C) but reached similar levels in the bacterial cytoplasm (Fig. 5D). As expected from data with the complemented mutant in vivo, expression of srcA in trans restored effector secretion in the srcA mutant (data not shown).\n"
],
"offsets": [
[
0,
2189
]
]
}
] | [
{
"id": "PMC2816692-02-Results-05_T1",
"type": "Protein",
"text": [
"SrcA"
],
"offsets": [
[
0,
4
]
],
"normalized": []
},
{
"id": "PMC2816692-02-Results-05_T2",
"type": "Protein",
"text": [
"SrcA"
],
"offsets": [
[
115,
119
]
],
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},
{
"id": "PMC2816692-02-Results-05_T3",
"type": "Protein",
"text": [
"SrcA"
],
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[
200,
204
]
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"id": "PMC2816692-02-Results-05_T4",
"type": "Protein",
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"SrcA"
],
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[
408,
412
]
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"normalized": []
},
{
"id": "PMC2816692-02-Results-05_T5",
"type": "Organism",
"text": [
"Salmonella"
],
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[
418,
428
]
],
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},
{
"id": "PMC2816692-02-Results-05_T6",
"type": "Protein",
"text": [
"srcA"
],
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498,
502
]
],
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},
{
"id": "PMC2816692-02-Results-05_T7",
"type": "Protein",
"text": [
"srcA"
],
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[
544,
548
]
],
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},
{
"id": "PMC2816692-02-Results-05_T8",
"type": "Organism",
"text": [
"srcA mutant"
],
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[
707,
718
]
],
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},
{
"id": "PMC2816692-02-Results-05_T9",
"type": "Protein",
"text": [
"srcA"
],
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[
707,
711
]
],
"normalized": []
},
{
"id": "PMC2816692-02-Results-05_T10",
"type": "Protein",
"text": [
"SrcA"
],
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[
1041,
1045
]
],
"normalized": []
},
{
"id": "PMC2816692-02-Results-05_T11",
"type": "Protein",
"text": [
"SseL"
],
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[
1197,
1201
]
],
"normalized": []
},
{
"id": "PMC2816692-02-Results-05_T12",
"type": "Protein",
"text": [
"SrcA"
],
"offsets": [
[
1271,
1275
]
],
"normalized": []
},
{
"id": "PMC2816692-02-Results-05_T13",
"type": "Protein",
"text": [
"SseL"
],
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[
1301,
1305
]
],
"normalized": []
},
{
"id": "PMC2816692-02-Results-05_T14",
"type": "Protein",
"text": [
"SrcA"
],
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[
1353,
1357
]
],
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},
{
"id": "PMC2816692-02-Results-05_T15",
"type": "Protein",
"text": [
"OmpF"
],
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[
1477,
1481
]
],
"normalized": []
},
{
"id": "PMC2816692-02-Results-05_T16",
"type": "Organism",
"text": [
"srcA mutant"
],
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[
1730,
1741
]
],
"normalized": []
},
{
"id": "PMC2816692-02-Results-05_T17",
"type": "Protein",
"text": [
"srcA"
],
"offsets": [
[
1730,
1734
]
],
"normalized": []
},
{
"id": "PMC2816692-02-Results-05_T18",
"type": "Protein",
"text": [
"SseL"
],
"offsets": [
[
1870,
1874
]
],
"normalized": []
},
{
"id": "PMC2816692-02-Results-05_T19",
"type": "Protein",
"text": [
"PipB2"
],
"offsets": [
[
1882,
1887
]
],
"normalized": []
},
{
"id": "PMC2816692-02-Results-05_T20",
"type": "Organism",
"text": [
"srcA mutant"
],
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[
1943,
1954
]
],
"normalized": []
},
{
"id": "PMC2816692-02-Results-05_T21",
"type": "Protein",
"text": [
"srcA"
],
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[
1943,
1947
]
],
"normalized": []
},
{
"id": "PMC2816692-02-Results-05_T22",
"type": "Protein",
"text": [
"srcA"
],
"offsets": [
[
2110,
2114
]
],
"normalized": []
},
{
"id": "PMC2816692-02-Results-05_T23",
"type": "Organism",
"text": [
"srcA mutant"
],
"offsets": [
[
2159,
2170
]
],
"normalized": []
},
{
"id": "PMC2816692-02-Results-05_T24",
"type": "Protein",
"text": [
"srcA"
],
"offsets": [
[
2159,
2163
]
],
"normalized": []
}
] | [
{
"id": "PMC2816692-02-Results-05_E1",
"type": "Binding",
"trigger": {
"text": [
"binds"
],
"offsets": [
[
5,
10
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMC2816692-02-Results-05_T1"
}
]
},
{
"id": "PMC2816692-02-Results-05_E2",
"type": "Localization",
"trigger": {
"text": [
"secreted"
],
"offsets": [
[
1914,
1922
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMC2816692-02-Results-05_T18"
}
]
},
{
"id": "PMC2816692-02-Results-05_E3",
"type": "Localization",
"trigger": {
"text": [
"secreted"
],
"offsets": [
[
1914,
1922
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMC2816692-02-Results-05_T19"
}
]
},
{
"id": "PMC2816692-02-Results-05_E4",
"type": "Gene_expression",
"trigger": {
"text": [
"reached"
],
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[
1975,
1982
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMC2816692-02-Results-05_T18"
}
]
},
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"id": "PMC2816692-02-Results-05_E5",
"type": "Gene_expression",
"trigger": {
"text": [
"reached"
],
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[
1975,
1982
]
]
},
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{
"role": "Theme",
"ref_id": "PMC2816692-02-Results-05_T19"
}
]
},
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"type": "Gene_expression",
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"text": [
"expression"
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2096,
2106
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]
},
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{
"role": "Theme",
"ref_id": "PMC2816692-02-Results-05_T22"
}
]
}
] | [] | [] |
5 | PMC1913099-02-Results-Discussion-06 | [
{
"id": "PMC1913099-02-Results-Discussion-06__text",
"type": "abstract",
"text": [
"Differential Expression of Genes from Diverse Functional Categories \nWe identified a number of genes encoding proteins involved in housekeeping processes (such as carbohydrate and coenzyme metabolism) that were differentially expressed, indicating a shift in metabolic processes due to host cell adherence (Tables 1 and 2). For example, genes encoding proteins involved in folate biosynthesis [40] were upregulated, suggesting that certain cofactors that may be necessary during adherence were unavailable. Also upregulated were genes encoding subunits of the F0F1 ATPase [41] (discussed in more detail later), which may indicate an acid stress response to maintain cytoplasmic pH or a need to generate ATP in response to increased energy requirements. We also identified the adherence-mediated upregulation of four transcriptional regulators (Table 1), suggestive of an adaptive response to host cell contact that is dynamic and complex. For example, RopB (encoded by spy2042), a member of the Rgg family of response regulators, interacts with a number of regulatory networks throughout the streptococcal genome (e.g., mga, csrRS, sagA, and fasBCA), affecting the transcription of numerous proteins, virulence factors, and two-component regulatory systems [42,43]. Although the delineation of genes influenced by RopB (or any identified transcriptional regulator) is beyond the scope of this study, our initial analysis did identify the upregulation of a two-component regulatory system, encoded by spy1236-1237. The functions of these particular loci are not yet known, and their adherence-mediated upregulation represents new targets in the study of regulators that function during host cell contact.\n"
],
"offsets": [
[
0,
1704
]
]
}
] | [
{
"id": "PMC1913099-02-Results-Discussion-06_T1",
"type": "Chemical",
"text": [
"folate"
],
"offsets": [
[
373,
379
]
],
"normalized": []
},
{
"id": "PMC1913099-02-Results-Discussion-06_T2",
"type": "Chemical",
"text": [
"ATP"
],
"offsets": [
[
703,
706
]
],
"normalized": []
},
{
"id": "PMC1913099-02-Results-Discussion-06_T3",
"type": "Protein",
"text": [
"RopB"
],
"offsets": [
[
952,
956
]
],
"normalized": []
},
{
"id": "PMC1913099-02-Results-Discussion-06_T4",
"type": "Protein",
"text": [
"spy2042"
],
"offsets": [
[
969,
976
]
],
"normalized": []
},
{
"id": "PMC1913099-02-Results-Discussion-06_T5",
"type": "Protein",
"text": [
"Rgg"
],
"offsets": [
[
995,
998
]
],
"normalized": []
},
{
"id": "PMC1913099-02-Results-Discussion-06_T6",
"type": "Protein",
"text": [
"mga"
],
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[
1120,
1123
]
],
"normalized": []
},
{
"id": "PMC1913099-02-Results-Discussion-06_T7",
"type": "Two-component-system",
"text": [
"csrRS"
],
"offsets": [
[
1125,
1130
]
],
"normalized": []
},
{
"id": "PMC1913099-02-Results-Discussion-06_T8",
"type": "Protein",
"text": [
"csrR"
],
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[
1125,
1129
]
],
"normalized": []
},
{
"id": "PMC1913099-02-Results-Discussion-06_T9",
"type": "Protein",
"text": [
"S"
],
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[
1129,
1130
]
],
"normalized": []
},
{
"id": "PMC1913099-02-Results-Discussion-06_T10",
"type": "Protein",
"text": [
"sagA"
],
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[
1132,
1136
]
],
"normalized": []
},
{
"id": "PMC1913099-02-Results-Discussion-06_T11",
"type": "Regulon-operon",
"text": [
"fasBCA"
],
"offsets": [
[
1142,
1148
]
],
"normalized": []
},
{
"id": "PMC1913099-02-Results-Discussion-06_T12",
"type": "Protein",
"text": [
"fasB"
],
"offsets": [
[
1142,
1146
]
],
"normalized": []
},
{
"id": "PMC1913099-02-Results-Discussion-06_T13",
"type": "Protein",
"text": [
"C"
],
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[
1146,
1147
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],
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},
{
"id": "PMC1913099-02-Results-Discussion-06_T14",
"type": "Protein",
"text": [
"A"
],
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]
],
"normalized": []
},
{
"id": "PMC1913099-02-Results-Discussion-06_T15",
"type": "Protein",
"text": [
"RopB"
],
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[
1314,
1318
]
],
"normalized": []
},
{
"id": "PMC1913099-02-Results-Discussion-06_T16",
"type": "Two-component-system",
"text": [
"spy1236-1237"
],
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[
1500,
1512
]
],
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},
{
"id": "PMC1913099-02-Results-Discussion-06_T17",
"type": "Protein",
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"spy1236"
],
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},
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"id": "PMC1913099-02-Results-Discussion-06_T18",
"type": "Protein",
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"1237"
],
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1508,
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],
"normalized": []
}
] | [
{
"id": "PMC1913099-02-Results-Discussion-06_E1",
"type": "Process",
"trigger": {
"text": [
"virulence"
],
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]
]
},
"arguments": []
},
{
"id": "PMC1913099-02-Results-Discussion-06_E2",
"type": "Positive_regulation",
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"text": [
"upregulation"
],
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMC1913099-02-Results-Discussion-06_T16"
}
]
}
] | [
{
"id": "PMC1913099-02-Results-Discussion-06_1",
"entity_ids": [
"PMC1913099-02-Results-Discussion-06_T4",
"PMC1913099-02-Results-Discussion-06_T3"
]
}
] | [] |
6 | PMC2682197-02-Results-04 | [
{
"id": "PMC2682197-02-Results-04__text",
"type": "abstract",
"text": [
"M. tuberculosis Rv2623 is a nucleotide-binding protein \nWe began a biochemical characterization of Rv2623 in order to gain insight into the relationship between the molecular structure/function of this USP and it's growth-regulatory properties. M. tuberculosis Rv2623 was expressed in E. coli and purified to homogeneity for biochemical studies. SDS-PAGE analysis of affinity-purified His6-Rv2623 revealed a single band that approximates the predicted molecular mass of approximately31.6 kDa, which was identified by immunoblotting as Rv2623 (Figure S3). Gel filtration analysis of native His6-Rv2623 revealed that the purified protein exists primarily as a single species with an apparent molecular mass of 61+/-1 kDa; suggesting that Rv2623 is a dimer under native conditions (Figure S3), an observation that was later confirmed using nano electrospray ionization (nano ESI) mass spectrometry (data not shown). The nucleotide-binding capacity of a subset of USPs was discovered following the observation that MJ0577, a single-domain USP from Methanococcus jannaschii, co-purifies and co-crystallizes with ATP [26]. On the basis of structures of ATP-binding and non-ATP-binding USPs, a G-2X-G-9X-G(S/T) motif was suggested to be essential for the binding of ATP [27]. The presence of this motif in each of the two tandem USP domains of Rv2623 [7] raised the possibility that this protein possesses ATP binding activity. An HPLC-based examination of supernatants from boiled samples of His6-Rv2623 demonstrated that His6-Rv2623 co-purifies with both ATP and ADP (Figure 5). Analysis of E. coli-expressed Rv2623 using nano ESI mass spectrometry also demonstrated that an ATP-saturated form of dimeric Rv2623 (composed of 2 bound ATP molecules per monomer) constitutes at least half of the purified sample (data not shown). Measurement of the binding stoichiometry, which comprised HPLC-based quantification of adenine nucleotides from the boiled supernatant and spectral analysis of heat denatured Rv2623 following reconstitution in 6 M guanidine-HCl, yields 1.4+/-0.2 nucleotide equivalents/monomer with an overall content of 86+/-4% ATP (14+/-4% ADP). Thus, Rv2623 binds endogenous adenine nucleotides in E. coli, and the association is sufficiently tight that nearly 75% of the nucleotide binding sites are occupied upon purification. Indeed, nucleotide did not completely dissociate from the protein following an extensive, two-week dialysis with multiple changes against nucleotide-free buffer (approximately 0.3 nucleotide equivalents per monomer remain). It is conceivable that the presence of ADP is the consequence of an Rv2623-associated ATP activity and this putative ATPase function is currently under investigation.\n"
],
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[
0,
2728
]
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] | [
{
"id": "PMC2682197-02-Results-04_T1",
"type": "Organism",
"text": [
"M. tuberculosis"
],
"offsets": [
[
0,
15
]
],
"normalized": []
},
{
"id": "PMC2682197-02-Results-04_T2",
"type": "Protein",
"text": [
"Rv2623"
],
"offsets": [
[
16,
22
]
],
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},
{
"id": "PMC2682197-02-Results-04_T3",
"type": "Protein",
"text": [
"Rv2623"
],
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99,
105
]
],
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},
{
"id": "PMC2682197-02-Results-04_T4",
"type": "Organism",
"text": [
"M. tuberculosis"
],
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[
245,
260
]
],
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},
{
"id": "PMC2682197-02-Results-04_T5",
"type": "Protein",
"text": [
"Rv2623"
],
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[
261,
267
]
],
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},
{
"id": "PMC2682197-02-Results-04_T6",
"type": "Organism",
"text": [
"E. coli"
],
"offsets": [
[
285,
292
]
],
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},
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"id": "PMC2682197-02-Results-04_T7",
"type": "Protein",
"text": [
"Rv2623"
],
"offsets": [
[
390,
396
]
],
"normalized": []
},
{
"id": "PMC2682197-02-Results-04_T8",
"type": "Protein",
"text": [
"Rv2623"
],
"offsets": [
[
535,
541
]
],
"normalized": []
},
{
"id": "PMC2682197-02-Results-04_T9",
"type": "Protein",
"text": [
"Rv2623"
],
"offsets": [
[
594,
600
]
],
"normalized": []
},
{
"id": "PMC2682197-02-Results-04_T10",
"type": "Protein",
"text": [
"Rv2623"
],
"offsets": [
[
736,
742
]
],
"normalized": []
},
{
"id": "PMC2682197-02-Results-04_T11",
"type": "Protein",
"text": [
"MJ0577"
],
"offsets": [
[
1011,
1017
]
],
"normalized": []
},
{
"id": "PMC2682197-02-Results-04_T12",
"type": "Organism",
"text": [
"Methanococcus jannaschii"
],
"offsets": [
[
1044,
1068
]
],
"normalized": []
},
{
"id": "PMC2682197-02-Results-04_T13",
"type": "Chemical",
"text": [
"ATP"
],
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[
1107,
1110
]
],
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},
{
"id": "PMC2682197-02-Results-04_T14",
"type": "Chemical",
"text": [
"ATP"
],
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[
1147,
1150
]
],
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},
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"id": "PMC2682197-02-Results-04_T15",
"type": "Chemical",
"text": [
"ATP"
],
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[
1167,
1170
]
],
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},
{
"id": "PMC2682197-02-Results-04_T16",
"type": "Chemical",
"text": [
"ATP"
],
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[
1259,
1262
]
],
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},
{
"id": "PMC2682197-02-Results-04_T17",
"type": "Protein",
"text": [
"Rv2623"
],
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[
1337,
1343
]
],
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},
{
"id": "PMC2682197-02-Results-04_T18",
"type": "Chemical",
"text": [
"ATP"
],
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[
1399,
1402
]
],
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},
{
"id": "PMC2682197-02-Results-04_T19",
"type": "Protein",
"text": [
"Rv2623"
],
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[
1491,
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]
],
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},
{
"id": "PMC2682197-02-Results-04_T20",
"type": "Protein",
"text": [
"Rv2623"
],
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1521,
1527
]
],
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},
{
"id": "PMC2682197-02-Results-04_T21",
"type": "Chemical",
"text": [
"ATP"
],
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[
1550,
1553
]
],
"normalized": []
},
{
"id": "PMC2682197-02-Results-04_T22",
"type": "Chemical",
"text": [
"ADP"
],
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[
1558,
1561
]
],
"normalized": []
},
{
"id": "PMC2682197-02-Results-04_T23",
"type": "Organism",
"text": [
"E. coli"
],
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[
1586,
1593
]
],
"normalized": []
},
{
"id": "PMC2682197-02-Results-04_T24",
"type": "Protein",
"text": [
"Rv2623"
],
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[
1604,
1610
]
],
"normalized": []
},
{
"id": "PMC2682197-02-Results-04_T25",
"type": "Chemical",
"text": [
"ATP"
],
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[
1670,
1673
]
],
"normalized": []
},
{
"id": "PMC2682197-02-Results-04_T26",
"type": "Protein",
"text": [
"Rv2623"
],
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[
1700,
1706
]
],
"normalized": []
},
{
"id": "PMC2682197-02-Results-04_T27",
"type": "Chemical",
"text": [
"ATP"
],
"offsets": [
[
1728,
1731
]
],
"normalized": []
},
{
"id": "PMC2682197-02-Results-04_T28",
"type": "Protein",
"text": [
"Rv2623"
],
"offsets": [
[
1997,
2003
]
],
"normalized": []
},
{
"id": "PMC2682197-02-Results-04_T29",
"type": "Chemical",
"text": [
"guanidine-HCl"
],
"offsets": [
[
2036,
2049
]
],
"normalized": []
},
{
"id": "PMC2682197-02-Results-04_T30",
"type": "Chemical",
"text": [
"ATP"
],
"offsets": [
[
2134,
2137
]
],
"normalized": []
},
{
"id": "PMC2682197-02-Results-04_T31",
"type": "Protein",
"text": [
"Rv2623"
],
"offsets": [
[
2159,
2165
]
],
"normalized": []
},
{
"id": "PMC2682197-02-Results-04_T32",
"type": "Organism",
"text": [
"E. coli"
],
"offsets": [
[
2206,
2213
]
],
"normalized": []
},
{
"id": "PMC2682197-02-Results-04_T33",
"type": "Chemical",
"text": [
"ADP"
],
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[
2600,
2603
]
],
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},
{
"id": "PMC2682197-02-Results-04_T34",
"type": "Protein",
"text": [
"Rv2623"
],
"offsets": [
[
2629,
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]
],
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},
{
"id": "PMC2682197-02-Results-04_T35",
"type": "Chemical",
"text": [
"ATP"
],
"offsets": [
[
2647,
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]
],
"normalized": []
},
{
"id": "PMC2682197-02-Results-04_T36",
"type": "Chemical",
"text": [
"ATP"
],
"offsets": [
[
2678,
2681
]
],
"normalized": []
}
] | [
{
"id": "PMC2682197-02-Results-04_E1",
"type": "Gene_expression",
"trigger": {
"text": [
"expressed"
],
"offsets": [
[
272,
281
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMC2682197-02-Results-04_T5"
}
]
},
{
"id": "PMC2682197-02-Results-04_E2",
"type": "Binding",
"trigger": {
"text": [
"binding"
],
"offsets": [
[
1151,
1158
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMC2682197-02-Results-04_T14"
}
]
},
{
"id": "PMC2682197-02-Results-04_E3",
"type": "Binding",
"trigger": {
"text": [
"binding"
],
"offsets": [
[
1171,
1178
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMC2682197-02-Results-04_T15"
}
]
},
{
"id": "PMC2682197-02-Results-04_E4",
"type": "Binding",
"trigger": {
"text": [
"binding"
],
"offsets": [
[
1248,
1255
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMC2682197-02-Results-04_T16"
}
]
},
{
"id": "PMC2682197-02-Results-04_E5",
"type": "Gene_expression",
"trigger": {
"text": [
"expressed"
],
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[
1594,
1603
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMC2682197-02-Results-04_T24"
}
]
},
{
"id": "PMC2682197-02-Results-04_E6",
"type": "Binding",
"trigger": {
"text": [
"binds"
],
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[
2166,
2171
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMC2682197-02-Results-04_T31"
}
]
},
{
"id": "PMC2682197-02-Results-04_E7",
"type": "Binding",
"trigger": {
"text": [
"associated"
],
"offsets": [
[
2636,
2646
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMC2682197-02-Results-04_T34"
},
{
"role": "Theme",
"ref_id": "PMC2682197-02-Results-04_T35"
}
]
}
] | [] | [] |
7 | PMC2639726-03-Discussion-01 | [
{
"id": "PMC2639726-03-Discussion-01__text",
"type": "abstract",
"text": [
"Discussion \nDuring systemic mouse infection, Salmonella processes multiple environmental cues via more than 14 regulators We performed virulence assays on 83 regulators previously identified as required for Salmonella enteriditis virulence by one or more negative selection experiments in various hosts including calves, chickens, and mice [13], [21]-[23]. The mutant strains devoid of 83 regulators were tested in three mouse virulence assays to identify a subset of 14 that were most highly attenuated in a systemic mouse infection model. These 14 regulators are very diverse including alternative sigma factors (rpoS and rpoE), two-component regulators (ompR/envZ, phoP/phoQ, and ssrA/ssrB), post-transcriptional regulators (csrA, hfq and smpB), a bending protein (ihf) and an assortment of other DNA binding proteins (fruR, spvR, crp, slyA, and hnr; see Table 1 for references). Salmonella follows a short course of infection after intraperitoneal infection, as we have used here, passing through the lymph nodes in the peritoneal cavity to the blood stream and then colonizing and replicating within the spleen and liver. During this entire trip the bacteria are located within cells either neutrophiles or monocytes although at lower numbers in B and T cells and dendritic cells of every subclass [16],[37],[38],[65],[66]. Because the bacteria are exclusively intracellular we tested the hypothesis that replication in macrophages could be a surrogate for systemic mouse infection. Mutations that were attenuated for growth in primary macrophages were also attenuated in the mouse but the converse was not always true. Next, we used expression profiling to define the regulatory pathways. Transcriptional profiles from intracellular bacteria at different times after infection are likely to match most closely the environments encountered by Salmonella during infection. However, isolation of RNA from intracellular bacteria was not used because we wished to test a spectrum of regulatory mutants several of which simply did not survive within cells long enough to allow RNA preparation. RNA was therefore prepared using four laboratory growth conditions two of which partially mimic the intracellular environment (acidic minimal media). We compared the transcriptional profiles we observed using laboratory growth conditions that mimic intracellular conditions, to those that have been performed during intracellular replication within J774 macrophage like cells. We computed the z-score for each Salmonella gene from our data and from the data provided by Eriksson et al. [67] thus providing a value that can be compared across different experiments. To compare the two sets of data we subtracted the z-scores computed from our data for AMM1 from that computed from expression profiles of intracellular Salmonella. As the expression pattern changes with time after infection we computed the difference for each time as well as an average for all three-time points reported (4, 8, and 12 hours after infection). There were 102 genes where the difference in z-score was 2 or greater, and 54 genes of 102 were annotated as putative, hypothetical, or conserved hypothetical. Four of the 5 most strongly differentially induced genes include magnesium transporters (mgtB and mgtC), an acid shock protein (STM1485), and a high affinity phosphate transporter (pstS) suggesting that the acidic minimal media we used may not be low enough in magnesium, phosphate, or may not be sufficiently acidic. Many genes are transcribed inside cells but may be only weakly transcribed or not at all transcribed in acidic minimal media. Examples of such genes include sifA and the operon STM3117-3120. This operon encodes some of the most abundantly expressed proteins by intracellular Salmonella. This result is striking, given that STM3117-3120 are not transcribed under a variety of in vitro conditions including AMM1 and 2 and the many conditions corresponding to the transcriptional profiles reported for microarrays archived in GEO ([68], J. McDermott and L Shi, Unpubl. Obs.). The nature of the inducing signal(s) that results in expression of these genes during intracellular growth is not known. The regulatory network controlling expression of the genes necessary for systemic infection is complex. In our transcriptional network each pink node represents a regulator (Figure 6 B) and lines represent positive or negative transcriptional interactions (positive in red and negative in blue). In E. coli most regulation has been shown to follow one of three motifs: feedforward in which a regulator controls a second regulator, single input in which a regulator uniquely controls a set of downstream genes, and so called dense overlapping regulons in which there are multiple regulatory inputs to a single operon [69]. A feedforward loop can act as an electronic \"AND-gate\" preventing expression except when two or more signals are sensed as we see for slyA (upstream) and ssrB (downstream); fruR (upstream) and crp (downstream). Many of these predicted relationships have been demonstrated already but some are new and merit further investigation. The single input motif is found in systems of genes that form a protein complex such as both of the type III secretion systems in Salmonella. For SPI-2 ssrB plays this role and for SPI-1 hilA is the central regulator. The multiple promoters located within SPI-2 presumably respond to differences in ssrB/slyA activation, perhaps establishing part of the temporal order of expression following phagocytosis of Salmonella. There are other regulators required for systemic infection in BALB/c mice, including those whose absence reduces viability without a compensating mutation (hns; [70]), those that require deletion of two unlinked genes for inactivation (ppGpp; reviewed in [71] and ydgT/hha [48]), or those that were simply missed in the screens (STM0410; [72]); these regulators will be included in subsequent analyses.\n"
],
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0,
5967
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]
}
] | [
{
"id": "PMC2639726-03-Discussion-01_T1",
"type": "Organism",
"text": [
"mouse"
],
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28,
33
]
],
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},
{
"id": "PMC2639726-03-Discussion-01_T2",
"type": "Organism",
"text": [
"Salmonella"
],
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[
45,
55
]
],
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},
{
"id": "PMC2639726-03-Discussion-01_T3",
"type": "Organism",
"text": [
"Salmonella enteriditis"
],
"offsets": [
[
207,
229
]
],
"normalized": []
},
{
"id": "PMC2639726-03-Discussion-01_T4",
"type": "Organism",
"text": [
"calves"
],
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[
313,
319
]
],
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},
{
"id": "PMC2639726-03-Discussion-01_T5",
"type": "Organism",
"text": [
"chickens"
],
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[
321,
329
]
],
"normalized": []
},
{
"id": "PMC2639726-03-Discussion-01_T6",
"type": "Organism",
"text": [
"mice"
],
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[
335,
339
]
],
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},
{
"id": "PMC2639726-03-Discussion-01_T7",
"type": "Organism",
"text": [
"mouse"
],
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[
421,
426
]
],
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},
{
"id": "PMC2639726-03-Discussion-01_T8",
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"text": [
"mouse"
],
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[
518,
523
]
],
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},
{
"id": "PMC2639726-03-Discussion-01_T9",
"type": "Protein",
"text": [
"rpoS"
],
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[
615,
619
]
],
"normalized": []
},
{
"id": "PMC2639726-03-Discussion-01_T10",
"type": "Protein",
"text": [
"rpoE"
],
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[
624,
628
]
],
"normalized": []
},
{
"id": "PMC2639726-03-Discussion-01_T11",
"type": "Two-component-system",
"text": [
"ompR/envZ"
],
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[
657,
666
]
],
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},
{
"id": "PMC2639726-03-Discussion-01_T12",
"type": "Protein",
"text": [
"ompR"
],
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[
657,
661
]
],
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},
{
"id": "PMC2639726-03-Discussion-01_T13",
"type": "Protein",
"text": [
"envZ"
],
"offsets": [
[
662,
666
]
],
"normalized": []
},
{
"id": "PMC2639726-03-Discussion-01_T14",
"type": "Two-component-system",
"text": [
"phoP/phoQ"
],
"offsets": [
[
668,
677
]
],
"normalized": []
},
{
"id": "PMC2639726-03-Discussion-01_T15",
"type": "Protein",
"text": [
"phoP"
],
"offsets": [
[
668,
672
]
],
"normalized": []
},
{
"id": "PMC2639726-03-Discussion-01_T16",
"type": "Protein",
"text": [
"phoQ"
],
"offsets": [
[
673,
677
]
],
"normalized": []
},
{
"id": "PMC2639726-03-Discussion-01_T17",
"type": "Two-component-system",
"text": [
"ssrA/ssrB"
],
"offsets": [
[
683,
692
]
],
"normalized": []
},
{
"id": "PMC2639726-03-Discussion-01_T18",
"type": "Protein",
"text": [
"ssrA"
],
"offsets": [
[
683,
687
]
],
"normalized": []
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}
] | [] | [] |
8 | PMC2593050-00-TIAB | [
{
"id": "PMC2593050-00-TIAB__text",
"type": "abstract",
"text": [
"The Two-Component Regulatory System VicRK is Important to Virulence of Streptococcus equi Subspecies equi \nThis study aims at evaluating the importance of the two-component regulatory system VicRK to virulence of the horse pathogen Streptococcus equi subspecies equi and the potential of a vicK mutant as a live vaccine candidate using mouse infection models. The vicK gene was deleted by gene replacement. The DeltavicK mutant is attenuated in virulence in both subcutaneous and intranasal infections in mice. DeltavicK grows less slowly than the parent strain but retains the ability of S. equi to resist to phagocytosis by polymorphoneuclear leukocytes, suggesting that the vicK deletion causes growth defect. DeltavicK infection protects mice against reinfection with a wild-type S. equi strain. Intranasal DeltavicK infection induces production of anti-SeM mucosal IgA and systemic IgG. These results indicate that VicRK is important to S. equi growth and virulence and suggest that DeltavicK has the potential to be developed as a live S. equi vaccine.\n"
],
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[
0,
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]
]
}
] | [
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"id": "PMC2593050-00-TIAB_T1",
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"text": [
"VicRK"
],
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[
36,
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]
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"id": "PMC2593050-00-TIAB_T2",
"type": "Protein",
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"VicR"
],
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36,
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]
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{
"id": "PMC2593050-00-TIAB_T3",
"type": "Protein",
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"K"
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40,
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]
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"Streptococcus equi Subspecies equi"
],
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[
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]
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},
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"id": "PMC2593050-00-TIAB_T5",
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],
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191,
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]
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"id": "PMC2593050-00-TIAB_T6",
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],
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]
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"id": "PMC2593050-00-TIAB_T7",
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"K"
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"id": "PMC2593050-00-TIAB_T9",
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364,
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"id": "PMC2593050-00-TIAB_T13",
"type": "Organism",
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"DeltavicK mutant"
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[
411,
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{
"id": "PMC2593050-00-TIAB_T14",
"type": "Protein",
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"vicK"
],
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[
416,
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"id": "PMC2593050-00-TIAB_T15",
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"mice"
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[
505,
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"id": "PMC2593050-00-TIAB_T16",
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"S. equi"
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"id": "PMC2593050-00-TIAB_T23",
"type": "Organism",
"text": [
"S. equi"
],
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[
784,
791
]
],
"normalized": []
},
{
"id": "PMC2593050-00-TIAB_T24",
"type": "Organism",
"text": [
"DeltavicK"
],
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[
811,
820
]
],
"normalized": []
},
{
"id": "PMC2593050-00-TIAB_T25",
"type": "Protein",
"text": [
"vicK"
],
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[
816,
820
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],
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},
{
"id": "PMC2593050-00-TIAB_T26",
"type": "Protein",
"text": [
"SeM"
],
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[
858,
861
]
],
"normalized": []
},
{
"id": "PMC2593050-00-TIAB_T27",
"type": "Protein",
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"IgA"
],
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[
870,
873
]
],
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},
{
"id": "PMC2593050-00-TIAB_T28",
"type": "Protein",
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"IgG"
],
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887,
890
]
],
"normalized": []
},
{
"id": "PMC2593050-00-TIAB_T29",
"type": "Two-component-system",
"text": [
"VicRK"
],
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[
920,
925
]
],
"normalized": []
},
{
"id": "PMC2593050-00-TIAB_T30",
"type": "Protein",
"text": [
"VicR"
],
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[
920,
924
]
],
"normalized": []
},
{
"id": "PMC2593050-00-TIAB_T31",
"type": "Protein",
"text": [
"K"
],
"offsets": [
[
924,
925
]
],
"normalized": []
},
{
"id": "PMC2593050-00-TIAB_T32",
"type": "Organism",
"text": [
"S. equi"
],
"offsets": [
[
942,
949
]
],
"normalized": []
},
{
"id": "PMC2593050-00-TIAB_T33",
"type": "Organism",
"text": [
"DeltavicK"
],
"offsets": [
[
988,
997
]
],
"normalized": []
},
{
"id": "PMC2593050-00-TIAB_T34",
"type": "Protein",
"text": [
"vicK"
],
"offsets": [
[
993,
997
]
],
"normalized": []
},
{
"id": "PMC2593050-00-TIAB_T35",
"type": "Organism",
"text": [
"S. equi"
],
"offsets": [
[
1042,
1049
]
],
"normalized": []
}
] | [
{
"id": "PMC2593050-00-TIAB_E1",
"type": "Regulation",
"trigger": {
"text": [
"Important"
],
"offsets": [
[
45,
54
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMC2593050-00-TIAB_E2"
},
{
"role": "Cause",
"ref_id": "PMC2593050-00-TIAB_T1"
}
]
},
{
"id": "PMC2593050-00-TIAB_E2",
"type": "Process",
"trigger": {
"text": [
"Virulence"
],
"offsets": [
[
58,
67
]
]
},
"arguments": [
{
"role": "Participant",
"ref_id": "PMC2593050-00-TIAB_T4"
}
]
},
{
"id": "PMC2593050-00-TIAB_E3",
"type": "Regulation",
"trigger": {
"text": [
"importance"
],
"offsets": [
[
141,
151
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMC2593050-00-TIAB_E4"
},
{
"role": "Cause",
"ref_id": "PMC2593050-00-TIAB_T5"
}
]
},
{
"id": "PMC2593050-00-TIAB_E4",
"type": "Process",
"trigger": {
"text": [
"virulence"
],
"offsets": [
[
200,
209
]
]
},
"arguments": [
{
"role": "Participant",
"ref_id": "PMC2593050-00-TIAB_T9"
}
]
},
{
"id": "PMC2593050-00-TIAB_E5",
"type": "Process",
"trigger": {
"text": [
"infection"
],
"offsets": [
[
342,
351
]
]
},
"arguments": []
},
{
"id": "PMC2593050-00-TIAB_E6",
"type": "Negative_regulation",
"trigger": {
"text": [
"attenuated"
],
"offsets": [
[
431,
441
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMC2593050-00-TIAB_E7"
}
]
},
{
"id": "PMC2593050-00-TIAB_E7",
"type": "Process",
"trigger": {
"text": [
"virulence"
],
"offsets": [
[
445,
454
]
]
},
"arguments": [
{
"role": "Participant",
"ref_id": "PMC2593050-00-TIAB_T13"
}
]
},
{
"id": "PMC2593050-00-TIAB_E8",
"type": "Process",
"trigger": {
"text": [
"infections"
],
"offsets": [
[
491,
501
]
]
},
"arguments": [
{
"role": "Participant",
"ref_id": "PMC2593050-00-TIAB_T13"
}
]
},
{
"id": "PMC2593050-00-TIAB_E9",
"type": "Process",
"trigger": {
"text": [
"resist"
],
"offsets": [
[
600,
606
]
]
},
"arguments": [
{
"role": "Participant",
"ref_id": "PMC2593050-00-TIAB_T18"
}
]
},
{
"id": "PMC2593050-00-TIAB_E10",
"type": "Process",
"trigger": {
"text": [
"infection"
],
"offsets": [
[
723,
732
]
]
},
"arguments": [
{
"role": "Participant",
"ref_id": "PMC2593050-00-TIAB_T20"
}
]
},
{
"id": "PMC2593050-00-TIAB_E11",
"type": "Negative_regulation",
"trigger": {
"text": [
"protects"
],
"offsets": [
[
733,
741
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMC2593050-00-TIAB_E12"
},
{
"role": "Cause",
"ref_id": "PMC2593050-00-TIAB_E10"
}
]
},
{
"id": "PMC2593050-00-TIAB_E12",
"type": "Process",
"trigger": {
"text": [
"reinfection"
],
"offsets": [
[
755,
766
]
]
},
"arguments": [
{
"role": "Participant",
"ref_id": "PMC2593050-00-TIAB_T23"
}
]
},
{
"id": "PMC2593050-00-TIAB_E13",
"type": "Process",
"trigger": {
"text": [
"infection"
],
"offsets": [
[
821,
830
]
]
},
"arguments": [
{
"role": "Participant",
"ref_id": "PMC2593050-00-TIAB_T24"
}
]
},
{
"id": "PMC2593050-00-TIAB_E14",
"type": "Positive_regulation",
"trigger": {
"text": [
"induces"
],
"offsets": [
[
831,
838
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMC2593050-00-TIAB_E16"
},
{
"role": "Cause",
"ref_id": "PMC2593050-00-TIAB_E13"
}
]
},
{
"id": "PMC2593050-00-TIAB_E15",
"type": "Positive_regulation",
"trigger": {
"text": [
"induces"
],
"offsets": [
[
831,
838
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMC2593050-00-TIAB_E17"
},
{
"role": "Cause",
"ref_id": "PMC2593050-00-TIAB_E13"
}
]
},
{
"id": "PMC2593050-00-TIAB_E16",
"type": "Gene_expression",
"trigger": {
"text": [
"production"
],
"offsets": [
[
839,
849
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMC2593050-00-TIAB_T27"
}
]
},
{
"id": "PMC2593050-00-TIAB_E17",
"type": "Gene_expression",
"trigger": {
"text": [
"production"
],
"offsets": [
[
839,
849
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMC2593050-00-TIAB_T28"
}
]
},
{
"id": "PMC2593050-00-TIAB_E18",
"type": "Regulation",
"trigger": {
"text": [
"important"
],
"offsets": [
[
929,
938
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMC2593050-00-TIAB_E19"
},
{
"role": "Cause",
"ref_id": "PMC2593050-00-TIAB_T29"
}
]
},
{
"id": "PMC2593050-00-TIAB_E19",
"type": "Process",
"trigger": {
"text": [
"virulence"
],
"offsets": [
[
961,
970
]
]
},
"arguments": [
{
"role": "Participant",
"ref_id": "PMC2593050-00-TIAB_T32"
}
]
}
] | [] | [] |
9 | PMC2774163-02-Results-01 | [
{
"id": "PMC2774163-02-Results-01__text",
"type": "abstract",
"text": [
"Results \nThe formation of biofilms has been proposed to be controlled in response to environmental signals [39]. Given that protein phosphorylation is a common modification system used in signal transduction that changes the function of proteins in response to environmental stimuli [38], we chose a phosphoproteomic approach for the detection and identification of regulatory pathways active following the transition to the surface attached mode of growth. Detection of differentially phosphorylated proteins over the course of biofilm formation While phosphoproteomic analyses have become widespread in studies of regulation, signaling, development, the characterization of bacterial species and host responses during pathogenesis [40]-[49], only a limited number of studies have demonstrated that bacterial phosphoproteomes are dynamic [44],[46],[48]. We therefore used a combination of 2D/PAGE and immunoblot analysis using commercially available anti-phospho Ser/Thr antibodies (see Suppl. Fig. S1A-B for an example) to probe for the presence of signal transduction events that occur over the course of biofilm formation. Immunoblots of whole cell extracts obtained from planktonic cells and biofilm cells representing five developmental stages (reversibly and irreversibly attached cells, maturation-1 and -2 and dispersion stage; following 8, 24, 72, 144, and 216 hr of growth, respectively, see [12],[50] for timing of biofilm stages) were thus analyzed for the presence of planktonic- and biofilm-specific phosphorylation events. The planktonic mode of growth coincided with 24 phosphorylated proteins that were not phosphorylated following the transition of P. aeruginosa to surface-associated mode of growth (Fig. 1A, stage-specific events). Additional stage-specific events were detected for biofilms differing in age. For instance, 8 hr and 24 hr old biofilms displayed 23 and 21 phosphorylation events, respectively, not detected at any other stage. Regardless of the biofilm developmental stage, 7 phosphorylation events were detected that were absent in planktonic cells (Fig. 1A, biofilm-specific events). In both modes of growth, 26 proteins were constitutively phosphorylated. In addition to biofilm stage-specific phosphorylation of proteins, protein phosphorylation events were detectable at more than one biofilm growth stage indicating that the transition to surface-associated growth coincides with distinct protein phosphorylation and dephosphorylation events. As shown in Fig. 1A, these phosphorylation events are subcategorized as occurring during the reversible and irreversible attachment, biofilm formation and maturation stage depending on when and for how long protein phosphorylation was detected. For instance, four proteins were phosphorylated both in planktonic and reversible attached cells (8 hr biofilms) but not at any other biofilm stage (Fig. 1A, reversible attachment) while 4 different proteins were phosphorylated only in planktonic cells and biofilm cells after 8 hr and 24 hr of growth under flowing conditions (Fig. 1A, irreversible attachment). Furthermore, evidence of proteins being dephosphorylated over the course of biofilm formation was detected. Multiple proteins were found to be dephosphorylated at either a single or at multiple stages over the course of biofilm formation and maturation (Fig. 1B). Moreover, the similarity of the biofilm phosphoproteome to the planktonic phosphorylation patterns decreased from 59% in 8-hr-old biofilms to 35% in 144-hr-old, mature biofilms. The reduced similarity in phosphorylation events between biofilms and planktonic cells was mainly due to biofilm specific phosphorylation events detected at one or more stages of development. Dispersion-stage biofilms (216-hr-old) shared 43% similarity with the phosphorylation patterns of planktonically-grown P. aeruginosa cells (not shown). The increase in similarity between the planktonic and the 216-hr-old biofilm phosphoproteomes is consistent with previous reports indicating that cells within dispersion-stage biofilms are returning to the planktonic mode of growth [12],[50]. Protein phosphorylation in bacteria is not restricted to serine and threonine amino acid residues; however, the analysis of phosphorylation events by immunoblotting is limited to the availability of anti-phospho Ser/Thr (and tyrosine) antibodies. We therefore also purified phosphorylated proteins using metal oxide affinity chromatography (MOAC, see Fig. S1), a gel-independent approach allowing for the enrichment of phosphoproteins independent of the phosphorylation site with an up to 100% specificity [51],[52], followed by cleavable isotope coded affinity tag (cICAT) labeling and analysis by liquid chromatography tandem mass spectrometry (LC-MS/MS). This quantitative mass spectrometric approach was used to analyze protein phosphorylation patterns of biofilm cells grown to the reversible, irreversible, maturation-1 and maturation-2 biofilm stages (8-, 24-, 7-2, and 144-hr-old biofilms, respectively [12]) in comparison to those of planktonic cells. Similarly to the results obtained via immunoblot analysis, the changes in phosphorylation events over the course of biofilm development detected using LC-MS-MS analysis appeared to be stage-specific (two examples are shown in Suppl. Fig. S2), with the similarity to the planktonic patterns decreasing from 72% in 8 hr biofilms to 38% in 144 hr biofilms (Fig. 1C). The overall stage-specific (de)phosphorylation events as well as the differences in the phosphoproteome were similar to those detected by immunoblot analysis using anti-Ser/Thr antibodies. This is the first description of the dynamic changes of the phosphoproteome occurring during biofilm development. The combination of approaches used here has not been previously used to identify phosphorylated proteins in biofilms.\n"
],
"offsets": [
[
0,
5869
]
]
}
] | [
{
"id": "PMC2774163-02-Results-01_T1",
"type": "Organism",
"text": [
"P. aeruginosa"
],
"offsets": [
[
1668,
1681
]
],
"normalized": []
},
{
"id": "PMC2774163-02-Results-01_T2",
"type": "Organism",
"text": [
"P. aeruginosa"
],
"offsets": [
[
3847,
3860
]
],
"normalized": []
}
] | [] | [] | [] |
10 | PMC2242835-02-Results-05 | [
{
"id": "PMC2242835-02-Results-05__text",
"type": "abstract",
"text": [
"Link between Mutation in phoP and Secretion of ESAT-6 \nAs PhoP fulfills important regulatory functions in M. tuberculosis [21,22], it was of primary interest to identify and study potential effector molecules whose involvement in host pathogen interaction were influenced by the point mutation in phoP of H37Ra. Since secreted proteins of the ESX-1 system of M. tuberculosis constitute a major interface between the bacterium and its host [23], we analyzed the different strains for their potential to induce T cell responses against ESAT-6 and its binding partner, the 10-kD culture filtrate protein CFP-10. Groups of C57BL/6 mice were subcutaneously inoculated with H37Rv, H37Ra, or one of three recombinant H37Ra strains complemented with phoP, fadE5, or rpsL, respectively. Two weeks after vaccination we assessed the interferon-gamma (IFN-gamma) production of splenocytes mounted against ESX-1 antigens or controls. As anticipated, all tested strains induced IFN-gamma production in response to purified protein derivative (PPD) but not to a control peptide (Mal-E), indicating successful vaccination (Figure 3). Most importantly, the various strains differed extensively in their potential to induce antigen specific T cell responses towards ESAT-6 and CFP-10. As shown in Figure 3, splenocytes from mice that were inoculated with H37Rv produced high amounts of IFN-gamma upon stimulation with ESAT-6 or CFP-10, whereas the responses of H37Ra, H37Ra::fadE5, and H37Ra::rpsL infected mice were extremely weak. In contrast, splenocytes from H37Ra::phoP inoculated mice showed very strong IFN-gamma production in response to incubation with ESAT-6 and CFP-10. Exactly the same trend was observed when a highly sensitive T cell hybridoma assay was used to investigate ESAT-6 secretion. This test is based on the presentation of the immunodominant epitope contained in the first 20 amino acids of ESAT-6 by H37Ra, recombinant H37Ra, or H37Rv infected bone marrow-derived dendritic cells (BM-DC) to an ESAT-6-specific T cell hybridoma (NB11), restricted by I-Ab. Figure 4A shows that infection of BM-DC with H37Ra or H37Ra::rpsL induced no stimulation of the hybridoma as judged by IL-2 production, while H37Ra::phoP or H37Rv triggered high amounts of IL-2 production in this very sensitive and specific test. All strains behaved comparably towards the Ag85A:241-260 control, emphasizing the specificity of the observed phenomenon for ESAT-6 (Figure 4B). To further evaluate the involvement of phoP and the ESX-1 system in immunogenicity, C57BL/6 mice were vaccinated with additional strains. Firstly, we constructed a partially diploid H37Ra knock-in strain carrying cosmid RD1-ppe68-ko that, in BCG yields the greatest amounts of ESAT-6 expression and secretion [24]. However, in H37Ra the presence of this cosmid could not increase the weak ESAT-6 and CFP-10 T cell responses (Figure 3B) in the splenocyte IFN-gamma assay. Secondly, we also tested the previously described M. tuberculosis MT103 phoP knock-out (ko) strain SO2 [14,25] in this assay and found that this strain induced a potent PPD response as previously reported [25]. However, in comparison to the corresponding MT103 wild-type strain, the SO2 strain showed a strongly reduced ESAT-6 and CFP-10 specific T cell response, corresponding to a similar low level as the H37Ra strain (Figure 3B). Altogether, our data obtained from multiple replicate experiments indicate that a direct link exists between a fully functional PhoP and the ability to generate T cell responses against ESAT-6 and CFP-10.\n"
],
"offsets": [
[
0,
3565
]
]
}
] | [
{
"id": "PMC2242835-02-Results-05_T1",
"type": "Protein",
"text": [
"phoP"
],
"offsets": [
[
25,
29
]
],
"normalized": []
},
{
"id": "PMC2242835-02-Results-05_T2",
"type": "Protein",
"text": [
"ESAT-6"
],
"offsets": [
[
47,
53
]
],
"normalized": []
},
{
"id": "PMC2242835-02-Results-05_T3",
"type": "Protein",
"text": [
"PhoP"
],
"offsets": [
[
58,
62
]
],
"normalized": []
},
{
"id": "PMC2242835-02-Results-05_T4",
"type": "Organism",
"text": [
"M. tuberculosis"
],
"offsets": [
[
106,
121
]
],
"normalized": []
},
{
"id": "PMC2242835-02-Results-05_T5",
"type": "Protein",
"text": [
"phoP"
],
"offsets": [
[
297,
301
]
],
"normalized": []
},
{
"id": "PMC2242835-02-Results-05_T6",
"type": "Organism",
"text": [
"H37Ra"
],
"offsets": [
[
305,
310
]
],
"normalized": []
},
{
"id": "PMC2242835-02-Results-05_T7",
"type": "Organism",
"text": [
"M. tuberculosis"
],
"offsets": [
[
359,
374
]
],
"normalized": []
},
{
"id": "PMC2242835-02-Results-05_T8",
"type": "Protein",
"text": [
"ESAT-6"
],
"offsets": [
[
534,
540
]
],
"normalized": []
},
{
"id": "PMC2242835-02-Results-05_T9",
"type": "Protein",
"text": [
"CFP-10"
],
"offsets": [
[
601,
607
]
],
"normalized": []
},
{
"id": "PMC2242835-02-Results-05_T10",
"type": "Organism",
"text": [
"C57BL/6 mice"
],
"offsets": [
[
619,
631
]
],
"normalized": []
},
{
"id": "PMC2242835-02-Results-05_T11",
"type": "Organism",
"text": [
"H37Rv"
],
"offsets": [
[
668,
673
]
],
"normalized": []
},
{
"id": "PMC2242835-02-Results-05_T12",
"type": "Organism",
"text": [
"H37Ra"
],
"offsets": [
[
675,
680
]
],
"normalized": []
},
{
"id": "PMC2242835-02-Results-05_T13",
"type": "Organism",
"text": [
"H37Ra"
],
"offsets": [
[
710,
715
]
],
"normalized": []
},
{
"id": "PMC2242835-02-Results-05_T14",
"type": "Protein",
"text": [
"phoP"
],
"offsets": [
[
742,
746
]
],
"normalized": []
},
{
"id": "PMC2242835-02-Results-05_T15",
"type": "Protein",
"text": [
"fadE5"
],
"offsets": [
[
748,
753
]
],
"normalized": []
},
{
"id": "PMC2242835-02-Results-05_T16",
"type": "Protein",
"text": [
"rpsL"
],
"offsets": [
[
758,
762
]
],
"normalized": []
},
{
"id": "PMC2242835-02-Results-05_T17",
"type": "Protein",
"text": [
"interferon-gamma"
],
"offsets": [
[
822,
838
]
],
"normalized": []
},
{
"id": "PMC2242835-02-Results-05_T18",
"type": "Protein",
"text": [
"IFN-gamma"
],
"offsets": [
[
840,
849
]
],
"normalized": []
},
{
"id": "PMC2242835-02-Results-05_T19",
"type": "Protein",
"text": [
"IFN-gamma"
],
"offsets": [
[
964,
973
]
],
"normalized": []
},
{
"id": "PMC2242835-02-Results-05_T20",
"type": "Protein",
"text": [
"ESAT-6"
],
"offsets": [
[
1248,
1254
]
],
"normalized": []
},
{
"id": "PMC2242835-02-Results-05_T21",
"type": "Protein",
"text": [
"CFP-10"
],
"offsets": [
[
1259,
1265
]
],
"normalized": []
},
{
"id": "PMC2242835-02-Results-05_T22",
"type": "Organism",
"text": [
"mice"
],
"offsets": [
[
1306,
1310
]
],
"normalized": []
},
{
"id": "PMC2242835-02-Results-05_T23",
"type": "Organism",
"text": [
"H37Rv"
],
"offsets": [
[
1337,
1342
]
],
"normalized": []
},
{
"id": "PMC2242835-02-Results-05_T24",
"type": "Protein",
"text": [
"IFN-gamma"
],
"offsets": [
[
1368,
1377
]
],
"normalized": []
},
{
"id": "PMC2242835-02-Results-05_T25",
"type": "Protein",
"text": [
"ESAT-6"
],
"offsets": [
[
1400,
1406
]
],
"normalized": []
},
{
"id": "PMC2242835-02-Results-05_T26",
"type": "Protein",
"text": [
"CFP-10"
],
"offsets": [
[
1410,
1416
]
],
"normalized": []
},
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{
"id": "PMC2242835-02-Results-05_1",
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]
}
] | [] |
11 | PMC2593050-04-DISCUSSION | [
{
"id": "PMC2593050-04-DISCUSSION__text",
"type": "abstract",
"text": [
"DISCUSSION \nVicK is essential in B. subtilis [2] and S. aureus [3] but not in S. pneumoniae [7], S. mutans [8], and S. pyogenes [6]. We successfully deleted the vicK gene of S. equi. Thus, VicK is not essential in S. equi. However, the DeltavicK mutant is attenuated in virulence in both mouse models of subcutaneous and intranasal S. equi infections, indicating that VicRK is important to virulence. The results provide the further evidence for the importance of VicRK to virulence of Gram-positive pathogens. S. equi DeltavicK mutant does not grow as well as the wild-type strain in both THY and blood, suggesting that the vicK deletion causes defect in growth, a plausible reason that likely contributes to the attenuation of S. equi virulence in the mouse infection models. This suggestion is further supported by the observations that both the wild-type and DeltavicK mutant strains are resistant to phagocytosis by PMNs, which suggest that VicRK is not required for the evasion of S. equi to the innate immunity. As introduced earlier, the various phenotypes have been described for the vicRK mutants of the various pathogens. Whether the phenotypes are specific to particular organisms is not known. The phenotypes of the S. equi DeltavicK mutant are similar to those of the S. pyogenes DeltavicK mutant [6], suggesting that the growth defect phenotype may be a common feature of the vicRK mutants of various Gram-positive pathogens. The DeltavicK mutant appears to possess the properties of a potential live vaccine. First, it is attenuated in virulence in the mouse infection models. Secondly, DeltavicK inoculation protects mice against subsequent infection with wild-type S. equi. Thirdly, most of the mice with intranasal DeltavicK infection produce mucosal IgA and systemic IgG specific to protective antigen SeM. However, whether DeltavicK can be an effective live vaccine and whether the DeltavicK mutant has any advantages over the current live S. equi vaccine require the test of the mutant in horses since S. equi does not naturally infect mice. We hope to perform this expensive test in future when funds are available\n"
],
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[
0,
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{
"id": "PMC2593050-04-DISCUSSION_T1",
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"VicK"
],
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[
12,
16
]
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{
"id": "PMC2593050-04-DISCUSSION_T2",
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"text": [
"B. subtilis"
],
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[
33,
44
]
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},
{
"id": "PMC2593050-04-DISCUSSION_T3",
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"S. aureus"
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53,
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{
"id": "PMC2593050-04-DISCUSSION_T4",
"type": "Organism",
"text": [
"S. pneumoniae"
],
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[
78,
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]
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},
{
"id": "PMC2593050-04-DISCUSSION_T5",
"type": "Organism",
"text": [
"S. mutans"
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] | [] | [] |
12 | PMC2581603-03-Discussion | [
{
"id": "PMC2581603-03-Discussion__text",
"type": "abstract",
"text": [
"Discussion \nInfections caused by P. aeruginosa continue to be a leading cause of mortality among immunocompromised patients. The ability of P. aeruginosa to form biofilms promotes survival of the bacteria in the presence of antimicrobials and host defense mechanisms and is thought to contribute significantly to its ability to survive long-term within the hostile environment of chronically-infected patients. Understanding the mechanisms underlying antibiotic resistance and especially biofilm-specific antimicrobial resistance is of significant importance in the development of new treatment options and/or strategies. We have identified a novel mechanism of biofilm-associated antibiotic resistance in which the presence of DNA in the extracellular matrix of biofilms creates a localized cation-limited environment that is detected by P. aeruginosa leading to the induction of LPS modification genes and resistance to antimicrobials. Magnesium limitation has long been known as an in vitro signal that induces resistance to CAPs in P. aeruginosa [59]. As an intracellular pathogen, the PhoPQ system of Salmonella typhimurium is activated by limiting magnesium in vitro and phoP-regulated genes are also induced after invasion of macrophages and epithelial cells [65]. These observations suggested that Mg2+ is limiting within host cells, but it was recently shown that vacuole acidification and low pH is the crucial environmental trigger of PhoPQ activation [66]. Many extracellular pathogens possess homologs of the cation-sensing PhoPQ TCS that responds to magnesium limitation and induces genes necessary for surviving this environmental challenge [65]. However, to date the identification of a relevant in vivo environment for P. aeruginosa which is cation limited has remained elusive. We have demonstrated that DNA-rich environments, such as biofilms, are cation limited. While Mg2+ limitation has been identified as a signal involved in induced resistance to aminoglycosides in P. aeruginosa [59], the contribution of the PhoPQ-regulated LPS modifications has not been clearly determined. PhoQ mutants, which constitutively express phoP and are constitutively resistant to cationic antimicrobial peptides, are also more resistant to aminoglycosides [43]. In S. typhimurium, PhoPQ regulates multiple LPS modifications that decrease the OM permeability to membrane cationic dyes, bile salts and antibiotics, including gentamicin [67]. We report here that DNA-induces aminoglycoside resistance in P. aeruginosa biofilms, and this resistance is partially dependent on the LPS modification operon PA3552-PA3559. The aminoarabinose modification likely blocks the self-promoted uptake of aminoglycosides, which normally bind and displace cations that crosslink adjacent LPS molecules [68]. Previous reports have documented the involvement of P. aeruginosa PmrAB [49] and the E. coli PmrAB homologs BasRS [69] in regulating the formation of an antimicrobial peptide-tolerant subpopulation within biofilms. In pure culture P. aeruginosa biofilms, genomic DNA localizes throughout the biofilm surface monolayer and surrounds the mushroom-shaped microcolonies [51]. This coincides with the localization of a CAP-tolerant subpopulation of bacteria that expresses the PA3552-PA3559 operon along the surface of mushroom-structured P. aeruginosa biofilms [49]. To date, it was thought unlikely that a biofilm environment may be cation limited. However, our data indicates that the presence of DNA in biofilms does indeed result in a cation-limited environment, resulting in the induction of the LPS modification operon PA3552-PA3559. To our knowledge this is the first report to identify the antimicrobial properties of DNA. Above certain concentrations (approximately0.5% (w/v)) extracellular DNA inhibited planktonic growth and biofilm formation. Recently, a novel host defense mechanism was discovered whereby stimulated neutrophils ejected a mesh-like net of intracellular DNA and proteins that functions to trap and kill pathogens [70]. The antimicrobial property of neutrophil nets was attributed to DNA-associated histones and other antimicrobial peptides [70]. However, our results demonstrate that above certain concentrations, the DNA itself is antimicrobial due to cation chelation. In principle, cation chelation by DNA is similar to another recently identified host defense mechanism, where the Mn2+ and Zn2+ metal chelation properties of the host innate-immune protein calprotectin was shown to limit Staphylococcus aureus growth in tissue abscesses [71]. Staining of peg-adhered biofilms indicated that DNA was present throughout the biofilm. (Fig 5B). This data supports the hypothesis that the release of genomic DNA by lysed cells following exposure to inhibitory concentrations of extracellular DNA may result in a continual release of DNA by dying cells and a DNA gradient within the biofilm. Our observation that DNA imposes a cation gradient in biofilm is also consistent with previous reports of oxygen and nutrient gradients within biofilms, which result in diverse physiological cellular states within a biofilm community [72]. Although DNA is toxic at high concentrations, it functions as a double-edged sword whereby sub-inhibitory DNA concentrations serve to protect bacteria from antibiotic exposure, either from the host immune response or from antimicrobial treatment. It has previously been reported that Mg2+ concentrations within the airway surface fluid are high (2.2 mM) [73],[74]. However, sputum samples from the lungs of CF patients have very high concentrations of DNA, up to 20 mg/ml (2% (w/v)) [75],[76]. It is likely that within the CF lung, localized cation limited environments exist within DNA-rich microcolonies. It is also known that CF airway fluid contains high levels of neutrophil defensins [77] and that sub-lethal doses of CAPs induce PA3553 gene expression, although independently of PhoPQ and PmrAB [45]. Therefore, it appears that there are multiple environmental signals in the CF lung that can induce the expression the PA3552-PA3559 operon, which may explain why many P. aeruginosa CF isolates show LPS modifications such as aminoarabinose addition to lipid A [78]. As many P. aeruginosa strains isolated from the CF lung overproduce the negatively charged EPS alginate, we hypothesized that alginate may also be a relevant in vivo signal inducing expression of the PA3552-PA3559 operon. However, induction of PA3553 gene expression does not occur in the presence of alginate (data not shown). The observation that DNA is present in the lungs of CF patients has prompted the use of DNAseI as a therapeutic agent to reduce the sputum viscosity and improve lung function [75],[76]. However, our data suggests that the success of DNAseI therapy may, in part, be attributed to the degradation of DNA and subsequent disarming of the PhoPQ/PmrAB response and antibiotic resistance mechanisms. While previous studies have shown the biofilm matrix to function as a diffusion barrier to antibiotics, these results demonstrate a novel function of the biofilm matrix component DNA, where the cation chelating properties of DNA in biofilms induces resistance to host-derived or therapeutic antimicrobials. Furthermore, these findings indicate that DNA-rich environments, such as bacterial biofilms or the CF lung, may represent the natural setting where bacterial growth is cation limited, and highlight the importance of the PhoPQ/PmrAB controlled response and LPS modifications in antibiotic resistance in biofilms.\n"
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] | [] | [] |
13 | PMC2266911-02-Results_and_Discussion-02-01-02 | [
{
"id": "PMC2266911-02-Results_and_Discussion-02-01-02__text",
"type": "abstract",
"text": [
"Hemolysins or hemagglutinin-related proteins \nThese extracellular toxins target red blood cells to provide access to iron, but often show activity against immune cells, thus contributing to the bacterial response to the immune system of hosts, including phagocytosis by insect blood cells [64]. Hemolysins or surface-associated adhesins, together with their transporters, are sometimes organized as two-partner secretion (TPS) systems, a specialized mechanism for the delivery of large exoproteins [65]. TPS systems have been characterized mainly in pathogenic bacteria, but are also present in other microorganisms. P. luminescens and Y. enterocolitica TPS systems include the calcium-independent hemolysin PhlA that is transported through the outer membrane and activated by PhlB. Remarkably, their expression is induced by low iron concentration as encountered in the insect host, and phlA/phlB are up-regulated at 18degreesC compared to 28degreesC in Y. ruckeri [66]. Eight other TPS systems are present in P. luminescens, namely Plu0225/Plu0226, Plu0548/Plu0549, Plu1149/Plu1150, Plu1367/Plu1368, Plu3064/Plu3065, Plu3125-3127/3128, Plu3667/Plu3668, and Plu3718/Plu3719, and further three genes for which the partner locus has not been identified (Fig. 4). In the genome of Y. enterocolitica, only three complete TPS systems are present, namely YE0479/YE0480, YE2407/YE2408, (YE4084)YE4085/YE4086, and YE3454 which lacks the activator partner. Except YE0479/YE0480, all have counterparts in the P. luminescens genome. Recently, we have shown that a luciferase reporter insertion into YE0480 is induced at low temperature [67], indicating that this TPS system might contribute to insect pathogenicity and possibly to the host-specificity of Y. enterocolitica. The genomes of both pathogens also carry three and five, respectively, further hemolysin/hemagglutinin-related proteins which are absent in the other pathogen (Fig. 4). FhaC which belongs to a family of hemolysin activator proteins related to ShlA from Serratia marcescens is present in both pathogens and also induced at low temperature [67]. The genome sequence of P. luminescens exhibits more toxin genes than found in any other bacterial genome sequenced yet, including the genome of Y. enterocolitica. Hemolysin-related factors and their transporters discussed above are an example for this redundancy. However, the majority of these P. luminescens toxins exhibit highly significant similarities to those of Y. enterocolitica, suggesting common progenitors of hemolysins. It is therefore tempting to speculate that hemolytic activities of bacteria had been evolved during the association with insects and then adapted to mammalian hosts. Although it can not be excluded that the hemolysins of Y. enterocolitica act on the immune systems of both the insect and the mammalian host, the genetic overlap of this group of virulence factor between both pathogens, and the low-temperature expression of YE0479/YE0480 and fhaC, indicates the presence of insect-specific hemolysins in the genome of Y. enterocolitica.\n"
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"id": "PMC2266911-02-Results_and_Discussion-02-01-02_T40",
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1350,
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"id": "PMC2266911-02-Results_and_Discussion-02-01-02_T41",
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"id": "PMC2266911-02-Results_and_Discussion-02-01-02_T43",
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1365,
1371
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1372,
1378
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},
{
"id": "PMC2266911-02-Results_and_Discussion-02-01-02_T45",
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"id": "PMC2266911-02-Results_and_Discussion-02-01-02_T46",
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],
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1500,
1514
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},
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],
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1745,
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1933,
1937
]
],
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},
{
"id": "PMC2266911-02-Results_and_Discussion-02-01-02_T57",
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"ShlA"
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2007,
2011
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],
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},
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"id": "PMC2266911-02-Results_and_Discussion-02-01-02_T58",
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2017,
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"Y. enterocolitica"
],
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3059,
3076
]
],
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}
] | [
{
"id": "PMC2266911-02-Results_and_Discussion-02-01-02_E1",
"type": "Localization",
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"text": [
"transported"
],
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[
721,
732
]
]
},
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{
"role": "Theme",
"ref_id": "PMC2266911-02-Results_and_Discussion-02-01-02_T5"
}
]
},
{
"id": "PMC2266911-02-Results_and_Discussion-02-01-02_E2",
"type": "Positive_regulation",
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"text": [
"activated"
],
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[
764,
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]
]
},
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{
"role": "Theme",
"ref_id": "PMC2266911-02-Results_and_Discussion-02-01-02_T5"
},
{
"role": "Cause",
"ref_id": "PMC2266911-02-Results_and_Discussion-02-01-02_T6"
}
]
},
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"expression"
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}
]
},
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"type": "Gene_expression",
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"expression"
],
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]
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}
]
},
{
"id": "PMC2266911-02-Results_and_Discussion-02-01-02_E5",
"type": "Positive_regulation",
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"text": [
"up-regulated"
],
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902,
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}
]
},
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"induced"
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}
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"virulence"
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]
}
] | [] | [] |
14 | PMC2565068-00-TIAB | [
{
"id": "PMC2565068-00-TIAB__text",
"type": "abstract",
"text": [
"Incompetence of Neutrophils to Invasive Group A streptococcus Is Attributed to Induction of Plural Virulence Factors by Dysfunction of a Regulator \nGroup A streptococcus (GAS) causes variety of diseases ranging from common pharyngitis to life-threatening severe invasive diseases, including necrotizing fasciitis and streptococcal toxic shock-like syndrome. The characteristic of invasive GAS infections has been thought to attribute to genetic changes in bacteria, however, no clear evidence has shown due to lack of an intriguingly study using serotype-matched isolates from clinical severe invasive GAS infections. In addition, rare outbreaks of invasive infections and their distinctive pathology in which infectious foci without neutrophil infiltration hypothesized us invasive GAS could evade host defense, especially neutrophil functions. Herein we report that a panel of serotype-matched GAS, which were clinically isolated from severe invasive but not from non-invaive infections, could abrogate functions of human polymorphnuclear neutrophils (PMN) in at least two independent ways; due to inducing necrosis to PMN by enhanced production of a pore-forming toxin streptolysin O (SLO) and due to impairment of PMN migration via digesting interleukin-8, a PMN attracting chemokine, by increased production of a serine protease ScpC. Expression of genes was upregulated by a loss of repressive function with the mutation of csrS gene in the all emm49 severe invasive GAS isolates. The csrS mutants from clinical severe invasive GAS isolates exhibited high mortality and disseminated infection with paucity of neutrophils, a characteristic pathology seen in human invasive GAS infection, in a mouse model. However, GAS which lack either SLO or ScpC exhibit much less mortality than the csrS-mutated parent invasive GAS isolate to the infected mice. These results suggest that the abilities of GAS to abrogate PMN functions can determine the onset and severity of invasive GAS infection.\n"
],
"offsets": [
[
0,
1992
]
]
}
] | [
{
"id": "PMC2565068-00-TIAB_T1",
"type": "Organism",
"text": [
"Invasive Group A streptococcus"
],
"offsets": [
[
31,
61
]
],
"normalized": []
},
{
"id": "PMC2565068-00-TIAB_T2",
"type": "Organism",
"text": [
"Group A streptococcus"
],
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[
148,
169
]
],
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},
{
"id": "PMC2565068-00-TIAB_T3",
"type": "Organism",
"text": [
"GAS"
],
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[
171,
174
]
],
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},
{
"id": "PMC2565068-00-TIAB_T4",
"type": "Organism",
"text": [
"invasive GAS"
],
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[
380,
392
]
],
"normalized": []
},
{
"id": "PMC2565068-00-TIAB_T5",
"type": "Organism",
"text": [
"invasive GAS"
],
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[
593,
605
]
],
"normalized": []
},
{
"id": "PMC2565068-00-TIAB_T6",
"type": "Organism",
"text": [
"invasive GAS"
],
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[
774,
786
]
],
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},
{
"id": "PMC2565068-00-TIAB_T7",
"type": "Organism",
"text": [
"GAS"
],
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[
896,
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]
],
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},
{
"id": "PMC2565068-00-TIAB_T8",
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"text": [
"human"
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],
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},
{
"id": "PMC2565068-00-TIAB_T9",
"type": "Protein",
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"streptolysin O"
],
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[
1172,
1186
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],
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},
{
"id": "PMC2565068-00-TIAB_T10",
"type": "Protein",
"text": [
"SLO"
],
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[
1188,
1191
]
],
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},
{
"id": "PMC2565068-00-TIAB_T11",
"type": "Protein",
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"interleukin-8"
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[
1246,
1259
]
],
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},
{
"id": "PMC2565068-00-TIAB_T12",
"type": "Protein",
"text": [
"ScpC"
],
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[
1334,
1338
]
],
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},
{
"id": "PMC2565068-00-TIAB_T13",
"type": "Protein",
"text": [
"csrS"
],
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[
1430,
1434
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],
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},
{
"id": "PMC2565068-00-TIAB_T14",
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"emm49"
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1451,
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},
{
"id": "PMC2565068-00-TIAB_T15",
"type": "Organism",
"text": [
"invasive GAS"
],
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[
1464,
1476
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],
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},
{
"id": "PMC2565068-00-TIAB_T16",
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"csrS mutants"
],
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1491,
1503
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],
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},
{
"id": "PMC2565068-00-TIAB_T17",
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"csrS"
],
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1491,
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{
"id": "PMC2565068-00-TIAB_T18",
"type": "Organism",
"text": [
"invasive GAS"
],
"offsets": [
[
1525,
1537
]
],
"normalized": []
},
{
"id": "PMC2565068-00-TIAB_T19",
"type": "Organism",
"text": [
"human"
],
"offsets": [
[
1663,
1668
]
],
"normalized": []
},
{
"id": "PMC2565068-00-TIAB_T20",
"type": "Organism",
"text": [
"invasive GAS"
],
"offsets": [
[
1669,
1681
]
],
"normalized": []
},
{
"id": "PMC2565068-00-TIAB_T21",
"type": "Organism",
"text": [
"mouse"
],
"offsets": [
[
1698,
1703
]
],
"normalized": []
},
{
"id": "PMC2565068-00-TIAB_T22",
"type": "Organism",
"text": [
"GAS"
],
"offsets": [
[
1720,
1723
]
],
"normalized": []
},
{
"id": "PMC2565068-00-TIAB_T23",
"type": "Protein",
"text": [
"SLO"
],
"offsets": [
[
1742,
1745
]
],
"normalized": []
},
{
"id": "PMC2565068-00-TIAB_T24",
"type": "Protein",
"text": [
"ScpC"
],
"offsets": [
[
1749,
1753
]
],
"normalized": []
},
{
"id": "PMC2565068-00-TIAB_T25",
"type": "Organism",
"text": [
"csrS-mutated parent invasive GAS"
],
"offsets": [
[
1791,
1823
]
],
"normalized": []
},
{
"id": "PMC2565068-00-TIAB_T26",
"type": "Protein",
"text": [
"csrS"
],
"offsets": [
[
1791,
1795
]
],
"normalized": []
},
{
"id": "PMC2565068-00-TIAB_T27",
"type": "Organism",
"text": [
"mice"
],
"offsets": [
[
1848,
1852
]
],
"normalized": []
},
{
"id": "PMC2565068-00-TIAB_T28",
"type": "Organism",
"text": [
"GAS"
],
"offsets": [
[
1898,
1901
]
],
"normalized": []
},
{
"id": "PMC2565068-00-TIAB_T29",
"type": "Organism",
"text": [
"invasive GAS"
],
"offsets": [
[
1968,
1980
]
],
"normalized": []
}
] | [
{
"id": "PMC2565068-00-TIAB_E1",
"type": "Process",
"trigger": {
"text": [
"Virulence"
],
"offsets": [
[
99,
108
]
]
},
"arguments": []
},
{
"id": "PMC2565068-00-TIAB_E2",
"type": "Process",
"trigger": {
"text": [
"infections"
],
"offsets": [
[
393,
403
]
]
},
"arguments": [
{
"role": "Participant",
"ref_id": "PMC2565068-00-TIAB_T4"
}
]
},
{
"id": "PMC2565068-00-TIAB_E3",
"type": "Process",
"trigger": {
"text": [
"infections"
],
"offsets": [
[
606,
616
]
]
},
"arguments": [
{
"role": "Participant",
"ref_id": "PMC2565068-00-TIAB_T5"
}
]
},
{
"id": "PMC2565068-00-TIAB_E4",
"type": "Process",
"trigger": {
"text": [
"infections"
],
"offsets": [
[
658,
668
]
]
},
"arguments": []
},
{
"id": "PMC2565068-00-TIAB_E5",
"type": "Process",
"trigger": {
"text": [
"infections"
],
"offsets": [
[
978,
988
]
]
},
"arguments": [
{
"role": "Participant",
"ref_id": "PMC2565068-00-TIAB_T7"
}
]
},
{
"id": "PMC2565068-00-TIAB_E6",
"type": "Gene_expression",
"trigger": {
"text": [
"production"
],
"offsets": [
[
1137,
1147
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMC2565068-00-TIAB_T9"
}
]
},
{
"id": "PMC2565068-00-TIAB_E7",
"type": "Positive_regulation",
"trigger": {
"text": [
"increased"
],
"offsets": [
[
1292,
1301
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMC2565068-00-TIAB_E8"
}
]
},
{
"id": "PMC2565068-00-TIAB_E8",
"type": "Gene_expression",
"trigger": {
"text": [
"production"
],
"offsets": [
[
1302,
1312
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMC2565068-00-TIAB_T12"
}
]
},
{
"id": "PMC2565068-00-TIAB_E9",
"type": "Process",
"trigger": {
"text": [
"infection"
],
"offsets": [
[
1589,
1598
]
]
},
"arguments": [
{
"role": "Participant",
"ref_id": "PMC2565068-00-TIAB_T16"
}
]
},
{
"id": "PMC2565068-00-TIAB_E10",
"type": "Process",
"trigger": {
"text": [
"infection"
],
"offsets": [
[
1682,
1691
]
]
},
"arguments": [
{
"role": "Participant",
"ref_id": "PMC2565068-00-TIAB_T20"
}
]
},
{
"id": "PMC2565068-00-TIAB_E11",
"type": "Process",
"trigger": {
"text": [
"infected"
],
"offsets": [
[
1839,
1847
]
]
},
"arguments": [
{
"role": "Participant",
"ref_id": "PMC2565068-00-TIAB_T22"
}
]
},
{
"id": "PMC2565068-00-TIAB_E12",
"type": "Process",
"trigger": {
"text": [
"infection"
],
"offsets": [
[
1981,
1990
]
]
},
"arguments": [
{
"role": "Participant",
"ref_id": "PMC2565068-00-TIAB_T29"
}
]
}
] | [
{
"id": "PMC2565068-00-TIAB_1",
"entity_ids": [
"PMC2565068-00-TIAB_T2",
"PMC2565068-00-TIAB_T3"
]
},
{
"id": "PMC2565068-00-TIAB_2",
"entity_ids": [
"PMC2565068-00-TIAB_T9",
"PMC2565068-00-TIAB_T10"
]
}
] | [] |
15 | PMC1913099-00-TIAB | [
{
"id": "PMC1913099-00-TIAB__text",
"type": "abstract",
"text": [
"Novel Algorithms Reveal Streptococcal Transcriptomes and Clues about Undefined Genes \nBacteria-host interactions are dynamic processes, and understanding transcriptional responses that directly or indirectly regulate the expression of genes involved in initial infection stages would illuminate the molecular events that result in host colonization. We used oligonucleotide microarrays to monitor (in vitro) differential gene expression in group A streptococci during pharyngeal cell adherence, the first overt infection stage. We present neighbor clustering, a new computational method for further analyzing bacterial microarray data that combines two informative characteristics of bacterial genes that share common function or regulation: (1) similar gene expression profiles (i.e., co-expression); and (2) physical proximity of genes on the chromosome. This method identifies statistically significant clusters of co-expressed gene neighbors that potentially share common function or regulation by coupling statistically analyzed gene expression profiles with the chromosomal position of genes. We applied this method to our own data and to those of others, and we show that it identified a greater number of differentially expressed genes, facilitating the reconstruction of more multimeric proteins and complete metabolic pathways than would have been possible without its application. We assessed the biological significance of two identified genes by assaying deletion mutants for adherence in vitro and show that neighbor clustering indeed provides biologically relevant data. Neighbor clustering provides a more comprehensive view of the molecular responses of streptococci during pharyngeal cell adherence.\n"
],
"offsets": [
[
0,
1718
]
]
}
] | [
{
"id": "PMC1913099-00-TIAB_T1",
"type": "Organism",
"text": [
"group A streptococci"
],
"offsets": [
[
440,
460
]
],
"normalized": []
},
{
"id": "PMC1913099-00-TIAB_T2",
"type": "Organism",
"text": [
"streptococci"
],
"offsets": [
[
1671,
1683
]
],
"normalized": []
}
] | [
{
"id": "PMC1913099-00-TIAB_E1",
"type": "Process",
"trigger": {
"text": [
"infection"
],
"offsets": [
[
261,
270
]
]
},
"arguments": []
},
{
"id": "PMC1913099-00-TIAB_E2",
"type": "Process",
"trigger": {
"text": [
"infection"
],
"offsets": [
[
511,
520
]
]
},
"arguments": []
}
] | [] | [] |
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Dataset Card for BioNLP 2011 ID
The dataset of the Infectious Diseases (ID) task of BioNLP Shared Task 2011.
Citation Information
@inproceedings{pyysalo-etal-2011-overview,
title = "Overview of the Infectious Diseases ({ID}) task of {B}io{NLP} Shared Task 2011",
author = "Pyysalo, Sampo and
Ohta, Tomoko and
Rak, Rafal and
Sullivan, Dan and
Mao, Chunhong and
Wang, Chunxia and
Sobral, Bruno and
Tsujii, Jun{'}ichi and
Ananiadou, Sophia",
booktitle = "Proceedings of {B}io{NLP} Shared Task 2011 Workshop",
month = jun,
year = "2011",
address = "Portland, Oregon, USA",
publisher = "Association for Computational Linguistics",
url = "https://aclanthology.org/W11-1804",
pages = "26--35",
}
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