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To survive and proliferate in the absence of oxygen, many enteric pathogens can undergo anaerobic respiration within the host by using nitrate (NO 3  - ) as an electron acceptor 1,2 . In these bacteria, NO 3  - is typically reduced by a nitrate reductase to nitrite (NO 2  - ), 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 NO 2  - 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, NO 3  - reduction in V. cholerae divergently affects bacterial fitness in a manner dependent on environmental pH. Remarkably, in alkaline conditions, V. cholerae can reduce NO 3  - to support population growth. Conversely, in acidic conditions, accumulation of NO 2  - from NO 3  - 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.

Anaerobic nitrate reduction divergently governs population expansion of the enteropathogen Vibrio cholerae