Clinical Relevance of Type II Fatty Acid Synthesis Bypass in Staphylococcus aureus

Author:

Gloux Karine1ORCID,Guillemet Mélanie1,Soler Charles2,Morvan Claire1,Halpern David1,Pourcel Christine3,Vu Thien Hoang3,Lamberet Gilles1,Gruss Alexandra1ORCID

Affiliation:

1. Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, France

2. Hôpital Percy, Clamart, France

3. Institute for Integrative Biology of the Cell, CNRS, Université Paris Sud, Université Paris-Saclay, Orsay, France

Abstract

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 pathogen Staphylococcus 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 veterinary S. aureus isolates. 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 the acc and fabD loci. We conclude that fatty-acid-dependent strategies to escape FASII inhibition are common among S. aureus isolates and correlate with anti-FASII resistance and emergence of nonculturable variants.

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

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