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Blue light (BL) is a major environmental factor that affects the physiology, behavior, and infectivity of bacteria as it contributes to the generation of reactive oxygen species (ROS) while increasing photo-oxidative stress in cells. However, precise photo-oxidative response mechanism in non-phototrophic bacteria is yet to be elucidated. In this study, we investigated the effect of BL in  Vibrio cholerae  by using genetics and transcriptome profiling. Genome-wide analysis revealed that transcription of 6.3% of  V. cholerae  genes were regulated by BL. We further showed that BL enhances ROS production, which is generated through the oxidative phosphorylation. To understand signaling mechanisms, we generated several knockouts and analyzed their transcriptome under BL exposure. Studies with a double-knockout confirm an anti-sigma factor (ChrR) and putative metalloregulatory-like protein (MerR) are responsible for the genome-wide regulation to BL response in  V. cholerae . Collectively, these results demonstrate that MerR-like proteins, in addition to ChrR, are required for  V. cholerae  to mount an appropriate response against photo-oxidative stress induced by BL. Outside its natural host,  V. cholerae  can survive for extended periods in natural aquatic environments. Therefore, the regulation of light response for  V. cholerae  may be a critical cellular process for its survival in these environments.

MerR and ChrR mediate blue light induced photo-oxidative stress response at the transcriptional level in Vibrio cholerae