Background
Pseudomonas aeruginosa relies on antioxidant enzymes to withstand host-derived oxidative stress during infection. Here, we investigated the role of bacterial glutathione peroxidase (GPx) in survival and virulence of the PA14 strain under inflammatory conditions associated with hyperuricemia.
Methods
Wild-type (WT) and Δgpx strains were exposed to isolated hypochlorous acid (HOCl), hydrogen peroxide (H₂O₂), tert-butyl hydroperoxide, and urate hydroperoxide (HOOU) or challenged with human neutrophils in the presence or absence of oxidative burst modulators. In vivo, normouricemic and potassium oxonate-induced hyperuricemic mice were intranasally infected with WT or Δgpx strains to assess bacterial burden, inflammation, oxidative damage, and survival.
Results
Deletion of gpx increased bacterial susceptibility to all oxidants, particularly HOOU, and significantly reduced survival in activated neutrophils. In mice, Δgpx infection resulted in reduced pulmonary bacterial burden, attenuated neutrophil infiltration, lower oxidative damage, and markedly improved survival compared to WT infection, an effect exacerbated by hyperuricemia in WT-infected animals. These findings demonstrate that GPx detoxifies organic hydroperoxides generated during inflammation, enhancing P. aeruginosa resistance to oxidative killing and promoting virulence.
Conclusion
Collectively, our results highlight the importance of redox regulation in bacterial pathogenesis and identify GPx as a potential target for redox-based anti-virulence strategies against multidrug-resistant P. aeruginosa.