PDF(Pubmed)
Abstract：
The gastrointestinal tract is densely colonized by a polymicrobial community known as the microbiota which serves as primary line of defence against pathogen invasion. The microbiota can limit gut-luminal pathogen growth at different stages of infection. This can be traced to specific commensal strains exhibiting direct or indirect protective functions. Although these mechanisms hold the potential to develop new approaches to combat enteric pathogens, they remain far from being completely described. In this study, we investigated how a mouse commensal Escherichia coli can outcompete Salmonella enterica serovar Typhimurium (S. Tm). Using a salmonellosis mouse model, we found that the commensal E. coli 8178 strain relies on a trojan horse trap strategy to limit S. Tm expansion in the inflamed gut. Combining mutants and reporter tools, we demonstrated that inflammation triggers the expression of the E. coli 8178 antimicrobial microcin H47 toxin which, when fused to salmochelin siderophores, can specifically alter S. Tm growth. This protective function was compromised upon disruption of the E. coli 8178 tonB-dependent catecholate siderophore uptake system, highlighting a previously unappreciated crosstalk between iron intake and microcin H47 activity. By identifying the genetic determinants mediating S. Tm competition, our work not only provides a better mechanistic understanding of the protective function displayed by members of the gut microbiota but also further expands the general contribution of microcins in bacterial antagonistic relationships. Ultimately, such insights can open new avenues for developing microbiota-based approaches to better control intestinal infections.
摘要：
胃肠道被称为微生物群的多微生物群落密集定植，该微生物群作为抵抗病原体入侵的主要防线。微生物群可以在感染的不同阶段限制肠腔病原体的生长。这可以追溯到表现出直接或间接保护功能的特定共生菌株。尽管这些机制有可能开发新的方法来对抗肠道病原体，他们仍然远远没有被完全描述。在这项研究中,我们研究了小鼠共生大肠杆菌如何胜过伤寒沙门氏菌（S.Tm）。使用沙门氏菌病小鼠模型，我们发现共生大肠杆菌8178菌株依赖于特洛伊木马陷阱策略来限制S.Tm在发炎的肠道中的扩张。结合突变体和记者工具，我们证明，炎症触发大肠杆菌8178抗菌microcinH47毒素的表达，当与salmochelin铁载体融合时，可以特异性地改变S.Tm的生长。这种保护功能在破坏大肠杆菌8178tonB依赖性儿茶酚铁载体摄取系统时受到损害，突出了铁摄入量和microcinH47活性之间以前未被重视的串扰。通过确定介导S.Tm竞争的遗传决定因素，我们的工作不仅提供了对肠道微生物群成员所表现出的保护功能的更好的机械理解，而且进一步扩大了微生物在细菌拮抗关系中的一般贡献。最终,这些见解可以为开发基于微生物群的方法以更好地控制肠道感染开辟新的途径。
