In vivo nitrosative stress-induced expression of a photolyase primes
Vibrio cholerae readies Vibrio cholerae for environmental blue light
Abstract
Bacterial pathogens possess the remarkable ability to sense and adapt to
their constantly changing environments. For example, Vibrio
cholerae, the causative agent of the severe diarrheal disease cholera,
thrives in aquatic settings and infects human hosts, employing dynamic
strategies to ensure survival between diverse environments. In this
study, we utilized RNA sequencing to investigate how V. cholerae
responds to nitric oxide (NO), a common stressor encountered during
infection. We found that cry1, encoding a photolyase, which
repairs DNA damage caused by exposure to blue light—a stressor found
in aquatic environments—was induced by NO. We observed that
cry1 was activated upon exposure to blue light and Cry1
contributed to mitigating blue light-induced reactive oxygen species
(ROS) production and stress responses. Cry1 is important for protecting
cells against blue light-induced cell death. Furthermore, we showed that
pre-induced Cry1 production, either by exposure to reactive nitrogen
species (RNS) in vitro or in mice, enhanced V. cholerae’s
resistance to blue light. Additionally, we found that V. cholerae
Cry1 and the E. coli ortholog PhrB were crucial in resisting
reactive oxygen species (ROS). Moreover, cry1 expression was
regulated by RpoE and the anti-sigma factor ChrR, with two cysteine
residues in ChrR playing vital roles in sensing RNS and blue
light-induced ROS, thereby modulating cry1 expression.
Collectively, our findings suggest that V. cholerae encounters
host-derived NO during infection, and the subsequent induction of Cry1
primes the bacterium effectively for challenges in aquatic environments
abundant in blue light once it exits the host gut.