Institute of Molecular Biology, Materials Science Institute and Department of Physics, The University of Oregon, Eugene, OR 97403.
School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA 30332.
Proc Natl Acad Sci U S A. 2018 Apr 17;115(16):E3779-E3787. doi: 10.1073/pnas.1720133115. Epub 2018 Apr 2.
Host-associated microbiota help defend against bacterial pathogens; however, the mechanisms by which pathogens overcome this defense remain largely unknown. We developed a zebrafish model and used live imaging to directly study how the human pathogen invades the intestine. The gut microbiota of fish monocolonized by symbiotic strain was displaced by expressing its type VI secretion system (T6SS), a syringe-like apparatus that deploys effector proteins into target cells. Surprisingly, displacement was independent of T6SS-mediated killing of , driven instead by T6SS-induced enhancement of zebrafish intestinal movements that led to expulsion of the resident microbiota by the host. Deleting an actin cross-linking domain from the T6SS apparatus returned intestinal motility to normal and thwarted expulsion, without weakening 's ability to kill in vitro. Our finding that bacteria can manipulate host physiology to influence intermicrobial competition has implications for both pathogenesis and microbiome engineering.
宿主相关的微生物群落有助于抵御细菌病原体；然而，病原体克服这种防御的机制在很大程度上仍然未知。我们开发了一种斑马鱼模型，并使用活体成像技术直接研究人类病原体如何入侵肠道。通过表达其类型六分泌系统（T6SS），一种将效应蛋白注入靶细胞的注射器样装置，使共生菌株单定植的鱼类肠道中 的菌群被取代。令人惊讶的是，这种取代与 T6SS 介导的杀伤无关，而是由 T6SS 诱导的增强的斑马鱼肠道运动所驱动，导致宿主排出常驻微生物群落。从 T6SS 装置中删除一个肌动蛋白交联结构域可使肠道运动恢复正常并阻止排出，而不会削弱 在体外杀死 的能力。我们的发现表明，细菌可以操纵宿主生理学来影响微生物间的竞争，这对发病机制和微生物组工程都有影响。
