AhrC and Eep Are Biofilm Infection-Associated Virulence Factors in Enterococcus faecalis
AhrC and Eep Are Biofilm Infection-Associated Virulence Factors in Enterococcus faecalis
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DOI：
10.1128/iai.01210-12
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发表时间：
2013-05-01
影响因子：
3.1
通讯作者：
Dunny, Gary M.
中科院分区：
文献类型：
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作者：
Frank, Kristi L.;Guiton, Pascale S.;Dunny, Gary M.
粪肠球菌是人类肠道微生物组的一部分，是卫生保健相关感染的主要原因。对多种大肠杆菌的致病机理进行了探讨。包括心内膜炎和导管相关性尿路感染（CANTITI）在内的粪便感染与临床分离株形成生物膜的能力有关。目的：鉴定大肠杆菌的染色体遗传决定因子。粪肠球菌生物膜介导的感染，我们使用心内膜炎的兔模型来测试在生物膜相关基因座中具有转座子插入或框内缺失的菌株：ahrC、argR、atlA、opuBC、pyrC、recN和sepF。只有ahrC突变体显着减弱心内膜炎。我们证明，转录调节AhrC和蛋白酶Eep，我们以前显示是一个心内膜炎毒力因子，也需要在小鼠EPTI的全毒力。因此，AhrC和Eep可被归类为肠球菌生物膜相关毒力因子。ahrC的丧失导致生物膜生物量早期附着和积累的缺陷。ahrC转录的表征表明，在野生型细胞中观察到的该位点的时间表达促进了早期生物膜形成和心内膜炎的建立。这是AhrC在任何细菌物种中作为毒力因子的首次报道。
Enterococcus faecalis is part of the human intestinal microbiome and is a prominent cause of health care-associated infections. The pathogenesis of many E. faecalis infections, including endocarditis and catheter-associated urinary tract infection (CAUTI), is related to the ability of clinical isolates to form biofilms. To identify chromosomal genetic determinants responsible for E. faecalis biofilm-mediated infection, we used a rabbit model of endocarditis to test strains with transposon insertions or in-frame deletions in biofilm-associated loci: ahrC, argR, atlA, opuBC, pyrC, recN, and sepF. Only the ahrC mutant was significantly attenuated in endocarditis. We demonstrate that the transcriptional regulator AhrC and the protease Eep, which we showed previously to be an endocarditis virulence factor, are also required for full virulence in murine CAUTI. Therefore, AhrC and Eep can be classified as enterococcal biofilm-associated virulence factors. Loss of ahrC caused defects in early attachment and accumulation of biofilm biomass. Characterization of ahrC transcription revealed that the temporal expression of this locus observed in wild-type cells promotes initiation of early biofilm formation and the establishment of endocarditis. This is the first report of AhrC serving as a virulence factor in any bacterial species.