Bacterial ornithine lipid, a surrogate membrane lipid under phosphate‐limiting conditions, plays important roles in bacterial persistence and interaction with host

Summary Ornithine lipids (OLs) are bacteria‐specific lipids that are found in the outer membrane of Gram (−) bacteria and increase as surrogates of phospholipids under phosphate‐limited environmental conditions. We investigated the effects of OL increase in bacterial membranes on pathogen virulence and the host immune response. In Pseudomonas aeruginosa, we increased OL levels in membranes by overexpressing the OL‐synthesizing operon (olsBA). These increases changed the bacterial surface charge and hydrophobicity, which reduced bacterial susceptibility to antibiotics and antimicrobial peptides (AMPs), interfered with the binding of macrophages to bacterial cells and enhanced bacterial biofilm formation. When grown under low phosphate conditions, P. aeruginosa became more persistent in the treatment of antibiotics and AMPs in an olsBA‐dependent manner. While OLs increased persistence, they attenuated P. aeruginosa virulence; in host cells, they reduced the production of inflammatory factors (iNOS, COX‐2, PGE2 and nitric oxide) and increased intracellular Ca2+ release. Exogenously added OL had similar effects on P. aeruginosa and host cells. Our results suggest that bacterial OL plays important roles in bacteria‐host interaction in a way that enhances bacterial persistence and develops chronic adaptation to infection.