A Peptidoglycan Amidase Activator Impacts Salmonella enterica Serovar Typhimurium Gut Infection
A Peptidoglycan Amidase Activator Impacts Salmonella enterica Serovar Typhimurium Gut Infection
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肽聚糖酰胺酶激活剂影响肠沙门氏菌鼠伤寒血清型肠道感染
DOI：
10.1128/iai.00187-20
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发表时间：
2020
影响因子：
3.1
通讯作者：
Miki Tsuyoshi
中科院分区：
文献类型：
--
作者：
Nakamura Nao;Hoshino Yusuke;Shiga Takuro;Haneda Takeshi;Okada Nobuhiko;Miki Tsuyoshi
鼠伤寒沙门氏菌是引起腹泻的重要食源性致病菌。S.鼠伤寒沙门氏菌通过与微生物群竞争来激发炎症反应并在肠腔中定殖。虽然关于潜在机制的证据正在积累，但感染阶段尚未得到充分定义。肽聚糖酰胺酶广泛分布于细菌中，并通过水解肽聚糖在肽聚糖维持中发挥重要作用。酰胺酶活化是调节两种同源活化剂NlpD或EnvC（也称为YibP）中的至少一种所必需的。最近的研究表明，肽聚糖酰胺酶AmiC介导的细胞分裂特异性地赋予了S.在发炎的肠道里发现了鼠伤寒。然而，它仍然是未知的同源激活剂参与的酰胺酶的激活和激活剂如何影响Salmonellasp。发病机制在这里，我们描述了两个激活剂，NlpD和EnvC，在鼠伤寒沙门氏菌细胞分裂和肠道感染的作用。EnvC参与了S.鼠伤寒沙门氏菌细胞通过激活AmiA和AmiC。TheenvC突变体在肠道感染中表现出损伤，包括肠道定植缺陷和引起炎症反应的能力降低。重要的是，envC突变体的定殖缺陷与微生物群无关，而是由S的减弱的运动性和趋化性赋予的。而在amiA amiC突变体中未观察到鼠伤寒沙门氏菌细胞。此外，envC突变体在诱导粘膜炎症和持续肠道定植方面受损。总的来说，我们的研究结果提供了一个新的洞察肽聚糖酰胺酶/同源激活剂电路和它们的依赖性发病机制。
Salmonella enterica serovar Typhimurium is an important foodborne pathogen that causes diarrhea. S. Typhimurium elicits inflammatory responses and colonizes the gut lumen by outcompeting the microbiota. Although evidence is accumulating with regard to the underlying mechanism, the infectious stage has not been adequately defined. Peptidoglycan amidases are widely distributed among bacteria and play a prominent role in peptidoglycan maintenance by hydrolyzing peptidoglycans. Amidase activation is required for the regulation of at least one of two cognate activators, NlpD or EnvC (also called YibP). Recent studies established that the peptidoglycan amidase AmiC-mediated cell division specifically confers a fitness advantage onS. Typhimurium in the inflamed gut. However, it remains unknown which cognate activators are involved in the amidase activation and how the activators influenceSalmonellasp. pathogenesis. Here, we characterize the role of two activators, NlpD and EnvC, inS. Typhimurium cell division and gut infection. EnvC was found to contribute to cell division ofS. Typhimurium cells through the activation of AmiA and AmiC. TheenvCmutant exhibited impairments in gut infection, including a gut colonization defect and reduced ability to elicit inflammatory responses. Importantly, the colonization defect of theenvCmutant was unrelated to the microbiota but was conferred by attenuated motility and chemotaxis ofS. Typhimurium cells, which were not observed in theamiA amiCmutant. Furthermore, theenvCmutant was impaired in its induction of mucosal inflammation and sustained gut colonization. Collectively, our findings provide a novel insight into the peptidoglycan amidase/cognate activator circuits and their dependent pathogenesis.