Pathogen Molecular Genetics Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, U.S. National Institutes of Health, 50 South Drive, Bethesda, MD 20814, USA.
Sci Transl Med. 2021 Nov 24;13(621):eabf4692. doi: 10.1126/scitranslmed.abf4692.
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. 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 mouse infection model with wild-type and isogenic mutant strains deficient in genes of the Fsr (fecal streptococci regulator) quorum-sensing system. We show that 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 spores blocked 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 pathogenesis is controlled by quorum sensing, which can be targeted with probiotic spores.
益生菌是否以及如何促进人类健康是一个有争议的问题。它们被声称的对抗胃肠道感染的益处主要与减少肠道微生物群中病原体的丰度有关。在机制上理解较少的是报道的益生菌在减少全身感染方面的价值。是一种机会性病原体，在通过肠道上皮细胞易位后会引起全身感染，特别是在接受抗生素治疗的住院和免疫功能低下的患者中。在这项研究中，我们使用了一种野生型和同源突变株缺乏 Fsr（粪便链球菌调节因子）群体感应系统基因的 感染小鼠模型。我们表明，通过产生蛋白酶 GelE，肠道到血液的 易位是由 Fsr 群体感应系统介导的，GelE 会损害肠道上皮细胞的完整性。此外，我们证明口服给予益生菌 孢子通过抑制 Fsr 活性阻断了从肠道到血液的 易位和随后的小鼠全身感染。这些发现表明，群体感应控制着 发病机制的一个关键方面，可以用益生菌 孢子作为靶点。
