The Periplasmic Nitrate Reductase NapABC Supports Luminal Growth of Salmonella enterica Serovar Typhimurium during Colitis
The Periplasmic Nitrate Reductase NapABC Supports Luminal Growth of Salmonella enterica Serovar Typhimurium during Colitis
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DOI：
10.1128/iai.00351-15
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发表时间：
2015-09-01
影响因子：
3.1
通讯作者：
Baeumler, Andreas J.
中科院分区：
文献类型：
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作者：
Lopez, Christopher A.;Rivera-Chvez, Fabian;Baeumler, Andreas J.
食源性病原体鼠伤寒沙门氏菌受益于急性炎症，部分原因是利用宿主来源的硝酸盐进行厌氧呼吸，并在肠腔生长过程中成功地与共生微生物竞争。鼠伤寒沙门氏菌基因组包含三种硝酸还原酶，由 narGHI、narZYV 和 napABC 基因编码。对大肠杆菌中存在的同源基因的研究表明，由 narGHI 基因编码的硝酸盐还原酶 A 是在厌氧环境中作为电子受体促进硝酸盐生长的主要酶。使用小鼠结肠炎模型，我们令人惊讶地发现，具有硝酸还原酶 A（narG 突变体）或在高浓度硝酸盐存在下诱导其转录的调节因子（narL 突变体）缺陷的鼠伤寒沙门氏菌菌株表现出与野生型鼠伤寒沙门氏菌相当的生长。相反，缺乏功能性周质硝酸还原酶（napA突变体）的菌株在结肠腔中表现出明显的生长缺陷。在大肠杆菌中，napABC 基因在低硝酸盐浓度存在的厌氧生长条件下转录最大化。 narP 编码一种响应调节因子，可响应低硝酸盐浓度激活 napABC 转录，其失活可显着减少肠腔中鼠伤寒沙门氏菌的生长。盲肠硝酸盐测量表明小鼠盲肠是硝酸盐有限的环境。总的来说，我们的结果表明鼠伤寒沙门氏菌利用周质硝酸盐还原酶来支持其在肠道中遇到的低硝酸盐浓度下的生长，这一策略可能与其他肠道病原体共有。
The food-borne pathogen Salmonella enterica serovar Typhimurium benefits from acute inflammation in part by using host-derived nitrate to respire anaerobically and compete successfully with the commensal microbes during growth in the intestinal lumen. The S. Typhimurium genome contains three nitrate reductases, encoded by the narGHI, narZYV, and napABC genes. Work on homologous genes present in Escherichia coli suggests that nitrate reductase A, encoded by the narGHI genes, is the main enzyme promoting growth on nitrate as an electron acceptor in anaerobic environments. Using a mouse colitis model, we found, surprisingly, that S. Typhimurium strains with defects in either nitrate reductase A (narG mutant) or the regulator inducing its transcription in the presence of high concentrations of nitrate (narL mutant) exhibited growth comparable to that of wild-type S. Typhimurium. In contrast, a strain lacking a functional periplasmic nitrate reductase (napA mutant) exhibited a marked growth defect in the lumen of the colon. In E. coli, the napABC genes are transcribed maximally under anaerobic growth conditions in the presence of low nitrate concentrations. Inactivation of narP, encoding a response regulator that activates napABC transcription in response to low nitrate concentrations, significantly reduced the growth of S. Typhimurium in the gut lumen. Cecal nitrate measurements suggested that the murine cecum is a nitrate-limited environment. Collectively, our results suggest that S. Typhimurium uses the periplasmic nitrate reductase to support its growth on the low nitrate concentrations encountered in the gut, a strategy that may be shared with other enteric pathogens.