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

Antimicrob Agents Chemother. 2017 Apr 24;61(5):e02515-16. doi: 10.1128/AAC.02515-16. Print 2017 May.

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.

Keywords: Staphylococcus aureus; antibiotic resistance; fatty acids; infection; nondetectable resistance; persistence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Infective Agents, Local / pharmacology*
  • Cattle
  • Drug Resistance, Bacterial / genetics
  • Fatty Acid Synthase, Type II / antagonists & inhibitors*
  • Fatty Acid Synthase, Type II / genetics
  • Fatty Acid Synthase, Type II / metabolism
  • Fatty Acid Synthesis Inhibitors / pharmacology*
  • Fatty Acids / metabolism
  • Humans
  • Microbial Sensitivity Tests
  • Staphylococcal Infections / drug therapy
  • Staphylococcal Infections / microbiology
  • Staphylococcus aureus / drug effects*
  • Staphylococcus aureus / isolation & purification
  • Staphylococcus aureus / metabolism
  • Triclosan / pharmacology*

Substances

  • Anti-Bacterial Agents
  • Anti-Infective Agents, Local
  • Fatty Acid Synthesis Inhibitors
  • Fatty Acids
  • Triclosan
  • Fatty Acid Synthase, Type II