Streptomycin-induced inflammation enhances Escherichia coli gut colonization through nitrate respiration.
Streptomycin-induced inflammation enhances Escherichia coli gut colonization through nitrate respiration.
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DOI：
10.1128/mbio.00430-13
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发表时间：
2013-07-02
期刊：
影响因子：
6.4
通讯作者：
Bäumler AJ
中科院分区：
文献类型：
--
作者：
Spees AM;Wangdi T;Lopez CA;Kingsbury DD;Xavier MN;Winter SE;Tsolis RM;Bäumler AJ
用链霉素处理增强了小鼠肠道中人源性大肠杆菌分离株的生长，这表明驻留的微生物群落（微生物群）可以抑制入侵微生物的生长，这种现象称为“定植抗性”。然而，链霉素治疗降低定殖抗性的确切机制仍然不清楚。在这里，我们表明链霉素治疗使小鼠更容易发生化学诱导的结肠炎，提高了抗生素可能通过改变粘膜免疫反应而不是通过防止微生物-微生物相互作用来降低定植抗性的可能性。对潜在机制的研究显示，链霉素治疗小鼠的盲肠粘膜中存在轻度炎症浸润，并伴有编码诱导型一氧化氮合酶的基因Nos 2表达升高。反过来，这种炎症反应以Nos 2依赖的方式通过硝酸盐呼吸增强大肠杆菌的管腔生长。这些数据确定了低水平的肠道炎症是链霉素治疗后对大肠杆菌定植丧失抗性的因素之一。我们的肠道是一个复杂的微生物群落的宿主，它通过教育免疫系统和提供生态位保护而带来益处。链霉素治疗对肠道群落的干扰通过未知机制降低了“定植抗性”。在这里，我们表明，链霉素增加了肠粘膜的炎症色调，从而使肠道更容易受到葡聚糖硫酸钠治疗，并通过硝酸盐呼吸促进Nos 2依赖性大肠杆菌的生长。这些数据表明，作为炎症宿主反应的副产物的替代电子受体的产生是负责降低对兼性厌氧菌如大肠杆菌定植的抗性的重要因素。
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. 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 mechanisms. Here we show that streptomycin increases the inflammatory tone of the intestinal mucosa, thereby making the bowel more susceptible to dextran sulfate sodium treatment and boosting the Nos2-dependent growth of commensal Escherichia coli by nitrate respiration. These data point to the generation of alternative electron acceptors as a by-product of the inflammatory host response as an important factor responsible for lowering resistance to colonization by facultative anaerobic bacteria such as E. coli.