title: Clinical Relevance of Type II Fatty Acid Synthesis Bypass in Staphylococcus aureus.
abstract: The need for new antimicrobials to treat bacterial infections has led to the use of type II fatty acid synthesis (FASII) enzymes as front-line targets. However, recent studies suggest that FASII inhibitors may not work against the opportunist pathogenStaphylococcus aureus, as environmental fatty acids favor emergence of multi-anti-FASII resistance. As fatty acids are abundant in the host and one FASII inhibitor, triclosan, is widespread, we investigated whether fatty acid pools impact resistance in clinical and veterinaryS. aureusisolates. Simple addition of fatty acids to the screening medium led to a 50% increase in triclosan resistance, as tested in 700 isolates. Moreover, nonculturable triclosan-resistant fatty acid auxotrophs, which escape detection under routine conditions, were uncovered in primary patient samples. FASII bypass in selected isolates correlated with polymorphisms in theaccandfabDloci. We conclude that fatty-acid-dependent strategies to escape FASII inhibition are common amongS. aureusisolates and correlate with anti-FASII resistance and emergence of nonculturable variants.
authors.affiliation: Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, France karine.gloux@inra.fr alexandra.gruss@inra.fr.
authors.forename: Karine
authors.identifier: 0000-0002-8880-6628
authors.initials: K
authors.lastname: Gloux
authors.affiliation: Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, France.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Guillemet
authors.affiliation: Hôpital Percy, Clamart, France.
authors.forename: Charles
authors.initials: C
authors.lastname: Soler
authors.affiliation: Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Morvan
authors.affiliation: Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, France.
authors.forename: David
authors.initials: D
authors.lastname: Halpern
authors.affiliation: Institute for Integrative Biology of the Cell, CNRS, Université Paris Sud, Université Paris-Saclay, Orsay, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Pourcel
authors.affiliation: Institute for Integrative Biology of the Cell, CNRS, Université Paris Sud, Université Paris-Saclay, Orsay, France.
authors.forename: Hoang
authors.initials: H
authors.lastname: Vu Thien
authors.affiliation: Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Lamberet
authors.affiliation: Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, France karine.gloux@inra.fr alexandra.gruss@inra.fr.
authors.forename: Alexandra
authors.identifier: 0000-0001-7426-5229
authors.initials: A
authors.lastname: Gruss
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000891:Anti-Infective Agents, Local / Q000494:pharmacology*; D002417:Cattle; D024881:Drug Resistance, Bacterial / Q000235:genetics; D054889:Fatty Acid Synthase, Type II / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D054872:Fatty Acid Synthesis Inhibitors / Q000494:pharmacology*; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D008826:Microbial Sensitivity Tests; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000302:isolation & purification / Q000378:metabolism; D014260:Triclosan / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D000891:Anti-Infective Agents, Local; D054872:Fatty Acid Synthesis Inhibitors; D005227:Fatty Acids; D014260:Triclosan; D054889:Fatty Acid Synthase, Type II
keywords: Staphylococcus aureus; antibiotic resistance; fatty acids; infection; nondetectable resistance; persistence