Biofilm formation by Pseudomonas aeruginosa facilitates chronic infection by avoiding immune clearance and reducing the efficacy of antimicrobial therapy. Now, Riquelme et al. find that P. aeruginosa utilizes itaconate, an abundant immunometabolite produced by myeloid cells in response to infection, to promote biofilm formation. Itaconate induces bacterial membrane stress, resulting in increases in anti-stress extracellular polysaccharide (EPS) expression and a decrease in lipopolysaccharide (LPS) expression. Itaconate-adapted P. aeruginosa accumulate mutations in the lptD gene, encoding a membrane protein that translocates LPS to the bacterial surface, leading to further substantial increases in EPS synthesis. In turn, EPS production stimulated even greater itaconate production by myeloid cells in mice. This metabolic adaptation in both pathogen and host skews infection towards chronic infection.