摘要

革兰氏阳性菌粪肠球菌（Enterococcus faecalis）既是胃肠道（GIT）的定植者又是严重医院感染的代理者。虽然它通常需要发病机制，但粪肠球菌对GIT的定植尚不清楚。粪肠球菌耐受高浓度的GIT抗菌剂，如胆酸盐和溶菌酶，导致我们推测对肠道抗菌素的抗性对于长期GIT定殖是必需的。显示出抗微生物耐药性缺陷的粪肠球菌突变体的分析显示，对于长期GIT定殖需要IreK，包膜完整性和抗微生物剂抗性的决定因素。 IreK是PASTA激酶蛋白家族的成员，细菌跨膜信号蛋白涉及细胞壁动态平衡的调节。在粪肠球菌的胆酸盐和溶菌酶抗性的几个决定因素中，IreK是唯一被发现是肠道定植所需的决定因素，强调该蛋白对肠球菌适应GIT的重要性。通过研究恢复定殖GIT能力的ΔireK抑制突变体，我们鉴定了两种保守的肠球菌蛋白（OG1RF_11271和OG1RF_11272），它们对IreK起拮抗作用并干扰细胞包膜完整性，抗微生物耐药性和GIT定植。我们的数据表明IreK通过其激酶活性抑制这些蛋白质的作用。 IreK，OG1RF_11271和OG1RF_11272存在于所有肠球菌中，表明它们对GIT定殖的影响在肠球菌中是普遍的。因此，我们已经定义了肠球菌核心基因组中的保守基因，通过它们对肠球菌包膜完整性和抗微生物剂抗性的影响来影响GIT定植。

The Gram-positive bacterium Enterococcus faecalis is both a colonizer of the gastrointestinal tract (GIT) and an agent of serious nosocomial infections. Although it is typically required for pathogenesis, GIT colonization by E. faecalis is poorly understood. E. faecalis tolerates high concentrations of GIT antimicrobials, like cholate and lysozyme, leading us to hypothesize that resistance to intestinal antimicrobials is essential for long-term GIT colonization. Analyses of E. faecalismutants exhibiting defects in antimicrobial resistance revealed that IreK, a determinant of envelope integrity and antimicrobial resistance, is required for long-term GIT colonization. IreK is a member of the PASTA kinase protein family, bacterial transmembrane signaling proteins implicated in the regulation of cell wall homeostasis. Among several determinants of cholate and lysozyme resistance in E. faecalis, IreK was the only one found to be required for intestinal colonization, emphasizing the importance of this protein to enterococcal adaptation to the GIT. By studying ΔireK suppressor mutants that recovered the ability to colonize the GIT, we identified two conserved enterococcal proteins (OG1RF_11271 and OG1RF_11272) that function antagonistically to IreK and interfere with cell envelope integrity, antimicrobial resistance, and GIT colonization. Our data suggest that IreK, through its kinase activity, inhibits the actions of these proteins. IreK, OG1RF_11271,
 and OG1RF_11272 are found in all enterococci, suggesting that their effect on GIT colonization is universal across enterococci. Thus, we have defined conserved genes in the enterococcal core genome that influence GIT colonization through their effect on enterococcal envelope integrity and antimicrobial resistance.

http://iai.asm.org/content/86/1/e00381-17.short