Geh-driven lipid metabolism at the host-pathogen interface in Staphylococcus aureus: Membrane remodeling,...

Staphylococcus aureus adaptation and persistence within host environments are strongly shaped by lipid availability and host-derived lipid fluxes encountered during infection. The glycerol ester hydrolase Geh, initially characterized as a secreted lipase hydrolyzing triacylglycerols and cholesteryl esters, is now emerging as a multifunctional enzyme operating at the host-lipid interface. By contributing to fatty acid release and re-esterification, Geh appears to participate in lipid flux and may thereby influence membrane composition and bacterial physiology. These Geh-associated processes have been linked to bacterial adaptation to both lipid-rich and lipotoxic conditions, modulation of susceptibility to antimicrobial fatty acids and antibiotics, biofilm formation, adhesion, and interactions with host immune defenses. Geh expression, secretion, and genomic organization, including prophage integration within the geh locus, are further associated with strain-dependent variability and host-associated specialization. Taken together, Geh-driven lipid metabolism appears to be an important determinant of S. aureus adaptation, antimicrobial tolerance, and persistence. This narrative review integrates current knowledge on Geh-centered lipid processes into a conceptual framework, identifies remaining knowledge gaps, and discusses implications for the development of new therapeutic strategies. The review also discusses these findings in relation to host-jump events, within a broader One Health perspective.