The Gb3-enriched CD59/flotillin plasma membrane domain regulates host cell invasion by Pseudomonas aeruginosa

Abstract The opportunistic pathogen Pseudomonas aeruginosa has gained precedence over the years due to its ability develop resistance existing antibiotics, thereby necessitating alternative strategies understand and combat bacterium. Our previous work identified interaction between bacterial lectin LecA host cell glycosphingolipid receptor globotriaosylceramide (Gb3) as a crucial step for engulfment of P. via lipid zipper mechanism. In this study, we define LecA-associated membrane domain by pull-down mass spectrometry analysis. We unraveled predilection binding saturated, long fatty acyl chain-containing Gb3 species in extracellular leaflet an induction dynamic phosphatidylinositol (3,4,5)-trisphosphate (PIP 3 ) clusters at intracellular co-localizing with sites binding. found flotillins GPI-anchored protein CD59 not only be integral part LecA-interacting domain, but also majorly influencing invasion depletion either these proteins resulted about 50% reduced invasiveness strain PAO1. summary, report that LecA-Gb3 induces formation plasma enriched saturated species, CD59, PIP flotillin facilitating efficient uptake