Syracuse

Permissive Fatty Acid Incorporation Promotes Staphylococcal Adaptation to FASII Antibiotics in Host Environments

Archive ouverte

Kénanian, Gérald | Morvan, Claire | Weckel, Antonin | Pathania, Amit | Anba-Mondoloni, Jamila | Halpern, David | Gaillard, Marine | Solgadi, Audrey | Dupont, Laetitia | Henry, Celine | Poyart, Claire | Fouet, Agnès | Lamberet, Gilles | Gloux, Karine | Gruss, Alexandra

Edité par CCSD ; Elsevier Inc -

International audience. 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

• Description
• Sujet/Public
• Outil
• Outil d'anticipation
• Mémoire et thèse
• Gestion