Diversity of Susceptibility to Unsaturated Fatty Acids in <i>Enterococcus</i> Strains and Their Synergistic Effects With Antibiotics

Enterococci are commensal bacteria in humans that are found in the intestine, pharynx and oral cavity and sometimes cause opportunistic infections such as intra-abdominal infections and bacteraemia. Several enterococcal species, especially E. faecium and E. faecalis, have become clinical problems as drug-resistant bacteria, including vancomycin-resistant Enterococci (VRE). Therefore, new antibacterial agents against enterococcal infections are needed. Because several fatty acids (FAs) have been reported to possess antibacterial activity, in this study, the effects of 3 unsaturated fatty acids on enterococci were evaluated using clinically isolated strains. Among the 3 fatty acids we tested, linoleic acid (LA) and palmitoleic acid (POA) exhibited antibacterial activity against E. faecalis and E. faecium. Next, we evaluated the antibacterial activities of the two FAs against 126 enterococcal clinical strains, including five different species. The minimum inhibitory concentration (MIC) of LA varied among bacterial species and strains (ranging from 37.5 to 1200 μM), while the MIC of POA was similar (ranging from 37.5 to 150 μM). Among species, E. faecium strains presented higher MICs than E. faecalis, E. avium and E. casseliflavus strains. In 6 VRE strains, the MICs of LA showed variable (150-1200 μM), whereas MICs of POA were constant at 75 μM. We subsequently investigated the combined effects of LA and POA with several antibiotics and found that LA had synergistic effects with β-lactam, gentamicin, ciprofloxacin and vancomycin against E. faecalis and E. faecium strains, including VRE, whereas POA did not have a significant effect. Our results indicate the potential application of FAs for enterococcal infection.