Pathogen adaptation to lung metabolites

Abstract

Opportunistic pathogens like Pseudomonas aeruginosa and Staphylococcus aureus rapidly adapt to the dynamic metabolic landscape of the respiratory mucosa during infection. Host phagocytes recognize these pathogens and trigger metabolic reprogramming, releasing immunometabolites such as succinate and itaconate. P. aeruginosa preferentially consumes succinate as a carbon source to enhance planktonic growth. In response to itaconate-induced membrane stress, it forms protective biofilms, allowing bacterial survival despite host defenses. Additionally, host ketone bodies support microbial communities that are less immunostimulatory and better tolerated by the lung. Similarly, S. aureus responds to itaconate by forming biofilms, aiding colonization in glucose-limited airways. In this milieu, S. aureus consumes proline, linking its survival with the metabolic activity of proline-producing fibroblasts. Here, we will review the competence of both P. aeruginosa and S. aureus to hijack host metabolic pathways, underscoring pathogen metabolic plasticity as an essential strategy to thrive in the human lung.