PvrA-Mediated Inhibition of Choline and Ethanolamine Uptake Promotes Pseudomonas aeruginosa Colonization in the Host Environment

Pseudomonas aeruginosa can utilize abundant phosphatidylcholine (PC) and phosphatidylethanolamine (PE) within the host as energy and structural substrates. Fatty acids, choline, and ethanolamine liberated from PC and PE can each serve as the sole carbon source to support bacterial growth in vitro. Our previous work demonstrated that fatty acid metabolism is critical for acute pulmonary infection caused by P. aeruginosa. The pathogen senses host-derived fatty acids via the transcriptional regulator PvrA, which activates fatty acid utilization pathways and drives the production of virulence factors required for acute infection. In this study, we demonstrate that during acute pulmonary infection in mice, P. aeruginosa upregulates fatty acid catabolism while simultaneously repressing choline and ethanolamine uptake and metabolism pathways. Deletion of the transcriptional activators GbdR and EatR (which control choline and ethanolamine utilization respectively) enhances pulmonary bacterial colonization. We further identify fatty acids as environmental signals that trigger repression of choline and ethanolamine utilization programs. PvrA mediates this signaling cascade by directly binding to the promoters of gbdR and eatR and suppressing their transcription upon fatty acid exposure.