Work

A choline-sensing regulator coordinates metabolic adaptation and pathogenesis in Pseudomonas aeruginosa pulmonary infections

Year: 2025

Type: article

Abstract: Pseudomonas aeruginosa exploits host-derived phosphatidylcholine (PC) to establish persistent lung infections, yet the mechanistic link between metabolic adaptation and pathogenesis remains unclear. Here, we demonstrate that choline (Cho)–induced regulator (CodR), a GcvA-type transcriptional regulator, serves as a master regulator integrating virulence, antibiotic resistance, and PC catabolism during pulmonary infection. CodR directly binds Cho, the key metabolite of PC degradation, to activate pchP and norA , facilitating exogenous PC/Cho utilization. Genome-wide profiling reveals that CodR targets conserved motifs in promoters of mexA , pslA , and amrZ , synchronizing virulence and tolerance pathways. codR deletion attenuated biofilm formation, type III secretion system activity, siderophore production, and PC catabolism, reducing bacterial pathogenicity in a murine pneumonia model. Notably, Cho/PC pretreatment potentiates CodR-dependent transcriptional activation of antibiotic resistance genes, elevating tolerance to ciprofloxacin and meropenem. Our findings elucidate a paradigm wherein P. aeruginosa co-opts host-derived Cho via CodR to simultaneously potentiate virulence and antibiotic resilience, exposing CodR as a druggable node to break infection-resistance synergies.

Source: Science Advances

DOI: 10.1126/sciadv.adz1415