BarA-UvrY two-component system regulates virulence of uropathogenic E. coli CFT073.

BarA-UvrY two-component system regulates virulence of uropathogenic E. coli CFT073.
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DOI:
10.1371/journal.pone.0031348
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Mukhopadhyay S
Mukhopadhyay S
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Palaniyandi S;Mitra A;Herren CD;Lockatell CV;Johnson DE;Zhu X;Mukhopadhyay S

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尿路致病性大肠杆菌(UPEC)是肠外致病性大肠杆菌的一种。大肠杆菌,导致约80%的社区获得性尿路感染(UTI)。UPEC以复杂的生命周期开始在尿路上皮细胞中定植,在细胞内和细胞外小生境中复制和持续存在。因此,UPEC引起膀胱炎和更严重的肾盂肾炎。为了进一步了解UPEC的毒力特性,我们研究了BarA-UvrY双组分系统(TCS)在UPEC毒力调控中的作用。我们的研究结果表明,BarA-UvrY TCS突变显着降低UPEC CFT 073的毒力,通过小鼠尿路感染,鸡胚杀伤试验,和对人肾脏和泌尿上皮细胞系的细胞毒性试验进行评估。此外,barA或uvrY基因突变减少溶血素、脂多糖(LPS)、促炎细胞因子(TNF-α和IL-6)和趋化因子(IL-8)的产生。此外,我们还讨论了BarA-UvrY TCS和CsrA在UPEC中正、负控制毒力的可能联系。总的来说,这项研究提供了BarA-UvrY TCS调节UPEC CFT 073毒力的证据,并可能指出以不同方式观察到的毒力调节机制可能控制UPEC在尿路中的长期存活。
Uropathogenic Escherichia coli (UPEC), a member of extraintestinal pathogenic E. coli, cause ∼80% of community-acquired urinary tract infections (UTI) in humans. UPEC initiates its colonization in epithelial cells lining the urinary tract with a complicated life cycle, replicating and persisting in intracellular and extracellular niches. Consequently, UPEC causes cystitis and more severe form of pyelonephritis. To further understand the virulence characteristics of UPEC, we investigated the roles of BarA-UvrY two-component system (TCS) in regulating UPEC virulence. Our results showed that mutation of BarA-UvrY TCS significantly decreased the virulence of UPEC CFT073, as assessed by mouse urinary tract infection, chicken embryo killing assay, and cytotoxicity assay on human kidney and uroepithelial cell lines. Furthermore, mutation of either barA or uvrY gene reduced the production of hemolysin, lipopolysaccharide (LPS), proinflammatory cytokines (TNF-α and IL-6) and chemokine (IL-8). The virulence phenotype was restored similar to that of wild-type by complementation of either barA or uvrY gene in trans. In addition, we discussed a possible link between the BarA-UvrY TCS and CsrA in positively and negatively controlling virulence in UPEC. Overall, this study provides the evidences for BarA-UvrY TCS regulates the virulence of UPEC CFT073 and may point to mechanisms by which virulence regulations are observed in different ways may control the long-term survival of UPEC in the urinary tract.
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