PA4933 Mediates Dual Regulation of Oxidative Resistance and Virulence in Pseudomonas aeruginosa Pulmonary Infection.

Pseudomonas aeruginosa is a critical opportunistic pathogen requiring rigorous prevention and control, which triggers severe infections in immunocompromised populations. Bacterial membrane proteins serve as core regulatory molecules coordinating stress tolerance and virulence homeostasis during host colonization. Nevertheless, the physiological functions of numerous structurally homologous yet unannotated membrane proteins remain largely elusive. In this study, we identified a significantly upregulated hypothetical gene, PA4933, from published transcriptomic datasets of P. aeruginosa PA14 infecting RAW264.7 macrophages. Bioinformatic prediction preliminarily confirmed that PA4933 is a highly conserved seven-transmembrane protein sharing high structural homology with ABC transporters. Mechanistically, PA4933 elevates the transcription of glnA to enrich intracellular glutamine, thereby markedly boosting glutathione (GSH) biosynthesis and enhancing bacterial antioxidant capacity. Meanwhile, PA4933 represses the transcription of virulence-related genes including phzC, rhlA, pel, motA, and motC, which consequently inhibits pyocyanin production, rhamnolipid synthesis, biofilm formation and swarming motility. Such regulatory effects alleviate bacterial damage to multiple infection models, including A549 alveolar epithelial cells, Galleria mellonella larvae and murine acute pneumonia models. Collectively, PA4933 exerts dual regulatory roles: facilitating antioxidant immune evasion while suppressing virulence and mitigating host tissue injury. This protein regulates the infection homeostasis of PAO1, it provides new insights into P. aeruginosa infection.