Anaerobic nitrate reduction divergently governs population expansion of the enteropathogen Vibrio cholerae
Anaerobic nitrate reduction divergently governs population expansion of the enteropathogen Vibrio cholerae
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DOI：
10.1038/s41564-018-0253-0
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发表时间：
2018-12-01
影响因子：
28.3
通讯作者：
Cava, Felipe
中科院分区：
文献类型：
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作者：
Bueno, Emilio;Sit, Brandon;Cava, Felipe
为了在缺氧条件下生存和增殖，许多肠道病原体可以通过使用硝酸盐（NO3-）作为电子受体在宿主体内进行无氧呼吸（1，2）。在这些细菌中，NO3-通常被硝酸盐还原酶还原为亚硝酸盐（NO2-），这是一种有毒的中间体，可被亚硝酸盐还原酶进一步还原（3）。然而，引起霍乱的肠道病原体霍乱弧菌缺乏亚硝酸盐还原酶，导致硝酸盐还原过程中NO2-积累。(4)因此，霍乱弧菌被认为不能进行NO（3）（-）（-）依赖性无氧呼吸（4）。在这里，我们表明，在缺氧的生长过程中，在V. cholesterol的NO3-减少分歧影响细菌的健身依赖于环境pH值的方式。值得注意的是，在碱性条件下，V. cholesterol可以减少NO3-，以支持人口增长。相反，在酸性条件下，NO3-还原产生的NO2-的积累同时限制了群体扩增，并通过降低发酵酸的产生来保持细胞活力。有趣的是，其他细菌物种，如鼠伤寒沙门氏菌，肠出血性大肠杆菌（EHEC）和啮齿类柠檬酸杆菌也复制了这种pH依赖性反应，这表明这种机制可能是保守的肠道病原体。我们的研究结果解释了细菌病原体如何利用单一的氧化还原反应，根据环境pH值的波动来调节种群扩张。
To survive and proliferate in the absence of oxygen, many enteric pathogens can undergo anaerobic respiration within the host by using nitrate (NO3-) as an electron acceptor(1,2). In these bacteria, NO3- is typically reduced by a nitrate reductase to nitrite (NO2-), a toxic intermediate that is further reduced by a nitrite reductase(3). However, Vibrio cholerae, the intestinal pathogen that causes cholera, lacks a nitrite reductase, leading to NO2- accumulation during nitrate reduction(.)(4) Thus, V. cholerae is thought to be unable to undergo NO(3)(-)(-)dependent anaerobic respiration(4). Here, we show that during hypoxic growth, NO3- reduction in V. cholerae divergently affects bacterial fitness in a manner dependent on environmental pH. Remarkably, in alkaline conditions, V. cholerae can reduce NO3- to support population growth. Conversely, in acidic conditions, accumulation of NO2- from NO3- reduction simultaneously limits population expansion and preserves cell viability by lowering fermentative acid production. Interestingly, other bacterial species such as Salmonella typhimurium, enterohaemorrhagic Escherichia coli (EHEC) and Citrobacter rodentium also reproduced this pH-dependent response, suggesting that this mechanism might be conserved within enteric pathogens. Our findings explain how a bacterial pathogen can use a single redox reaction to divergently regulate population expansion depending on the fluctuating environmental pH.