Cytochrome bd-II oxidase CyxA promotes the pathogenicity of Klebsiella pneumoniae by resisting oxidative stress.

Adaptation to oxidative stress is crucial for survival of Klebsiella pneumoniae in external environments and within infected hosts. Cytochrome bd oxidase contributes to oxidative stress resistance and enhances the pathogenicity of several pathogens. In this study, we explored the role of cytochrome bd-II oxidase CyxA in K. pneumoniae's response to oxidative stress and its overall pathogenicity. The expression level of cyxA was significantly increased in response to oxidative stress in the wild-type strain (WT). Deletion of cyxA reduced K. pneumoniae's resistance to exogenous hydrogen peroxide (H2O2) and nitric oxide (NO). Additionally, the expression levels of cyxA at 37°C and 41°C were significantly higher compared to 30°C, and the ΔcyxA strain exhibited significantly lower viable counts, elevated intracellular reactive oxygen species (ROS) levels, and decreased total antioxidant capacity (T-AOC) relative to WT at 37°C and 41°C. Results from intraperitoneal and intestinal infection models in mice revealed that CyxA promotes pathogenicity by enhancing the invasiveness of K. pneumoniae into intra-abdominal tissues and confers a fitness advantage in the inflamed gut. Moreover, we provide preliminary evidence that CyxA exhibits catalase activity and increases the expression of catalase KatE. In summary, our results suggest that cytochrome bd-II oxidase CyxA enhances K. pneumoniae's resistance to oxidative stress caused by exogenous ROS, elevated temperature, and inflammation, either by directly or indirectly metabolizing H2O2, thereby promoting its growth and pathogenicity.