Permissive Fatty Acid Incorporation Promotes Staphylococcal Adaptation to FASII Antibiotics in Host Environments
Résumé
The essentiality of fatty acid synthesis (FASII) prod-ucts in the human pathogenStaphylococcus aureusis the underlying rationale for FASII-targeted antimi-crobial drug design. Reports of anti-FASII efficacyin animals support this choice. However, restrictedtest conditions used previously led us to investigatethis postulate in a broader, host-relevant context.We report thatS. aureusrapidly adapts to FASIIantibiotics without FASII mutations when exposedto host environments. FASII antibiotic administrationupon signs of infection, rather than just after inocu-lation as commonly practiced, fails to eliminateS. aureusin a septicemia model.In vitro, serumlowersS. aureusmembrane stress, leading to agreater retention of the substrates required forenvironmental fatty acid (eFA) utilization: eFAs andthe acyl carrier protein. In this condition, eFA oc-cupies both phospholipid positions, regardless ofanti-FASII selection. Our results identifyS. aureusmembrane plasticity in host environments as amain limitation for using FASII antibiotics in mono
Domaines
Bactériologie
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