Deletion of NADH oxidase in Listeria monocytogenes promotes the bacterial infection of brain

Abstract

NADH oxidase (NOX) plays important roles in respiration and reactive oxygen species (ROS) generation in cells. In this study, we explored the function of NOX in Listeria monocytogenes by gene deletion. From our results, nox mutant strain (∆nox) had lower H₂O₂ level and showed no significant alteration in bacteria growth activity. But it had enhanced invasiveness during the invasion of glial cells and mice brain compared to wildtype strain. Furthermore, several virulence genes involved in invasion, such as inlA, inlB, vip and sigB, were upregulated in ∆nox, and the alterations could be restored by complementation. To explore if nox was involved in the interaction of pathogen and host, we examined the generation of host ROS including superoxide and H₂O₂ during infection, and found ∆nox invasion leading to less superoxide and H₂O₂ generation. Besides, the upregulation of pro-inflammatory factors in glial cells was restrained when invaded by ∆nox compared to wildtype and complementary strain. In conclusion, our study evaluated the function of nox in L. monocytogenes and indicated that nox could regulate the invasion of L. monocytogenes by regulating virulence genes expression and the interaction of host-and- pathogens.

Keywords: Brain invasion; Deletion; Inflammatory factors; NADH oxidase; Reactive oxygen species.