Whether and how probiotics promote human health is a controversial issue. Their claimed benefit for counteracting gastrointestinal infection is linked predominantly to reducing pathogen abundance within the intestinal microbiota. Less understood mechanistically is the reported value that probiotics could have in reducing systemic infections. Enterococcus faecalis is an opportunistic pathogen that causes systemic infection after translocation through the intestinal epithelium, particularly in hospitalized and immune-depleted patients receiving antibiotic therapy. In this study, we used an E. faecalis mouse infection model with wild-type and isogenic mutant strains deficient in genes of the E. faecalis Fsr (fecal streptococci regulator) quorum-sensing system. We show that E. faecalis translocation from the mouse gut into the blood is mediated by the Fsr quorum-sensing system through production of the protease GelE, which compromises intestinal epithelium integrity. Furthermore, we demonstrate that orally administered probiotic Bacillus subtilis spores blocked E. faecalis translocation from the gut to the bloodstream and subsequent systemic infection in mice by inhibiting Fsr activity. These findings demonstrate that a key aspect of Enterococcus pathogenesis is controlled by quorum sensing, which can be targeted with probiotic Bacillus spores.

中文翻译：

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口服益生菌芽孢杆菌可预防小鼠肠球菌菌血症

益生菌是否以及如何促进人类健康是一个有争议的问题。他们声称的对抗胃肠道感染的好处主要与减少肠道微生物群内的病原体丰度有关。据报道，益生菌在减少全身感染方面可能具有的价值在机制上鲜为人知。粪肠球菌是一种机会性病原体，通过肠上皮易位后引起全身感染，特别是在接受抗生素治疗的住院患者和免疫衰竭患者中。在这项研究中，我们使用了粪肠球菌小鼠感染模型，该模型具有粪肠球菌基因缺陷的野生型和同基因突变株。Fsr（粪便链球菌调节剂）群体感应系统。我们表明，从小鼠肠道到血液的粪肠球菌易位是由 Fsr 群体感应系统通过产生蛋白酶 GelE 介导的，这会损害肠道上皮的完整性。此外，我们证明口服益生菌枯草芽孢杆菌孢子通过抑制 Fsr 活性阻止了粪肠球菌从肠道到血液的易位和随后的小鼠全身感染。这些发现表明，肠球菌发病机制的一个关键方面是由群体感应控制的，这可以用益生菌芽孢杆菌孢子来靶向。