The LysR-type regulator LeuO regulates the acid tolerance response in Vibrio cholerae
The LysR-type regulator LeuO regulates the acid tolerance response in Vibrio cholerae
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DOI：
10.1099/mic.0.000194
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发表时间：
2015-12-01
期刊：
影响因子：
2.8
通讯作者：
Bina, James E.
中科院分区：
文献类型：
--
作者：
Ante, Vanessa M.;Bina, X. Renee;Bina, James E.
霍乱弧菌是一种嗜中性的肠道病原体，对酸极为敏感。当霍乱弧菌通过宿主胃肠道时，它暴露在各种环境压力下，包括低pH值和挥发性脂肪酸。暴露于酸性环境诱导霍乱弧菌耐酸反应的表达。耐酸反应的一个关键组成部分是cad系统，它由cadC和cadBA操纵子编码。CadB是一种赖氨酸/尸胺反转运蛋白，CadA是一种赖氨酸脱羧酶，它们共同起作用，对抗细胞内和细胞外的低ph值。CadC是一种膜相关转录因子，在酸性条件下激活cadBA的表达。本文研究了lysr型转录调节因子LeuO在霍乱弧菌耐酸反应中的作用。转录报告基因实验显示，leuO表达抑制cadC转录，表明leuO是cadC的抑制因子。与此一致的是，leuO表达与赖氨酸脱羧酶的产生呈负相关，leuO过表达导致对有机酸的敏感性增加。在cadA突变体中，leuO的过表达增强了有机酸的杀伤作用，这表明leuO在耐酸反应中的功能超出了对cad系统的调节。总的来说，这些研究已经确定了LeuO在霍乱弧菌耐酸性中的新的生理作用。
Vibrio cholerae is a neutrophilic enteric pathogen that is extremely sensitive to acid. As V. cholerae passages through the host gastrointestinal tract it is exposed to a variety of environmental stresses including low pH and volatile fatty acids. Exposure to acidic environments induces expression of the V. cholerae acid tolerance response. A key component of the acid tolerance response is the cad system, which is encoded by cadC and the cadBA operon. CadB is a lysine/cadaverine antiporter and CadA is a lysine decarboxylase and these function together to counter low intracellular and extracellular pH. CadC is a membrane-associated transcription factor that activates cadBA expression in response to acidic conditions. Herein we investigated the role of the LysR-type transcriptional regulator LeuO in the V. cholerae acid tolerance response. Transcriptional reporter assays revealed that leuO expression repressed cadC transcription, indicating that LeuO was a cadC repressor. Consistent with this, leuO expression was inversely linked to lysine decarboxylase production and leuO overexpression resulted in increased sensitivity to organic acids. Overexpression of leuO in a cadA mutant potentiated killing by organic acids, suggesting that the function of leuO in the acid tolerance response extended beyond its regulation of the cad system. Collectively, these studies have identified a new physiological role for LeuO in V. cholerae acid tolerance.