摘要

粪肠球菌既是人体胃肠道常见的共生菌，也是医院获得性感染的主要原因。多重耐药肠球菌的系统性感染发生在胃肠定植后。因此，预防多药耐药粪肠球菌的定殖可能是限制感染的有效方法。然而，关于粪肠球菌用于定殖和竞争稳定的胃肠生态位的机制尚不清楚。编码细菌素的信息素应答接合质粒在肠球菌菌株中是常见的，并且可以调节肠球菌之间或肠球菌与肠道微生物群之间的小生境竞争。我们开发了一种粪肠球菌定植模型，在不破坏微生物群的情况下，评价表达接合性质粒pPD1的细菌素21在肠球菌定植中的作用。在这里，我们显示携带pPD1的粪肠球菌替代本土肠球菌并且缺乏pPD1的粪肠球菌。此外，在肠道中，pPD1通过缀合转移到其他粪肠球菌菌株，增强了它们的存活。携带偶联缺陷型pPD1突变体的粪肠球菌菌株的定殖随后导致万古霉素抗性肠球菌的清除，而没有质粒转移。因此，共生细菌的细菌素表达可以影响胃肠道中的小生境竞争，并且由占据精确肠道细菌生态位的共生体递送的细菌素可能是特异性地消除多重耐药细菌的肠内定植的有效治疗方法，没有深度破坏的土着微生物群。

Enterococcus faecalis is both a common commensal of the human gastrointestinal tract and a leading cause of hospital-acquired infections1. Systemic infections with multidrug-resistant enterococci occur subsequent to gastrointestinal colonization2. Preventing colonization by multidrug-resistant E. faecalis could therefore be a valuable approach towards limiting infection. However, little is known about the mechanisms E. faecalis uses to colonize and compete for stable gastrointestinal niches. Pheromone-responsive conjugative plasmids encoding bacteriocins are common among enterococcal strains3 and could modulate niche competition among enterococci or between enterococci and the intestinal microbiota. We developed a model of colonization of the mouse gut with E. faecalis, without disrupting the microbiota, to evaluate the role of the conjugative plasmid pPD1 expressing bacteriocin 21 (ref. 4) in enterococcal colonization. Here we show that E. faecalis harbouring pPD1 replaces indigenous enterococci and outcompetes E. faecalis lacking pPD1. Furthermore, in the intestine, pPD1 is transferred to other E. faecalisstrains by conjugation, enhancing their survival. Colonization with an E. faecalis strain carrying a conjugation-defective pPD1 mutant subsequently resulted in clearance of vancomycin-resistant enterococci, without plasmid transfer. Therefore, bacteriocin expression by commensal bacteria can influence niche competition in the gastrointestinal tract, and bacteriocins, delivered by commensals that occupy a precise intestinal bacterial niche, may be an effective therapeutic approach to specifically eliminate intestinal colonization by multidrug-resistant bacteria, without profound disruption of the indigenous microbiota.

https://www.nature.com/articles/nature15524