Streptomycin-Induced Inflammation Enhances Escherichia coli Gut Colonization Through Nitrate Respiration

作者：Alanna M. Spees, Tamding Wangdi, Christopher A. Lopez, Dawn D. Kingsbury, Mariana N. Xavier, Sebastian Winter, Renée M. Tsolis, Andreas J. Bäumler · 发表于：mBio · 年份：2013 · DOI：10.1128/mbio.00430-13 · 被引用次数：255 · 研究领域：Gut microbiota and health、Bacterial Genetics and Biotechnology、Escherichia coli research studies

UNLABELLED: Treatment with streptomycin enhances the growth of human commensal Escherichia coli isolates in the mouse intestine, suggesting that the resident microbial community (microbiota) can inhibit the growth of invading microbes, a phenomenon known as "colonization resistance." However, the precise mechanisms by which streptomycin treatment lowers colonization resistance remain obscure. Here we show that streptomycin treatment rendered mice more susceptible to the development of chemically induced colitis, raising the possibility that the antibiotic might lower colonization resistance by changing mucosal immune responses rather than by preventing microbe-microbe interactions. Investigation of the underlying mechanism revealed a mild inflammatory infiltrate in the cecal mucosa of streptomycin-treated mice, which was accompanied by elevated expression of Nos2, the gene that encodes inducible nitric oxide synthase. In turn, this inflammatory response enhanced the luminal growth of E. coli by nitrate respiration in a Nos2-dependent fashion. These data identify low-level intestinal inflammation as one of the factors responsible for the loss of resistance to E. coli colonization after streptomycin treatment. IMPORTANCE: Our intestine is host to a complex microbial community that confers benefits by educating the immune system and providing niche protection. Perturbation of intestinal communities by streptomycin treatment lowers "colonization resistance" through unknown mechan...