Inhibition of Staphylococcus aureus Biofilm Formation and Virulence Factor Production by Petroselinic Acid and Other Unsaturated C18 Fatty Acids

Staphylococcus aureus is a major human pathogen that secretes several toxins associated with the pathogenesis of sepsis and pneumonia. Its antibiotic resistance is notorious, and its biofilms play a critical role in antibiotic tolerance. We hypothesized fatty acids might inhibit S. aureus biofilm formation and the expressions of its virulence factors. Initially, the antibiofilm activities of 27 fatty acids against a methicillin-sensitive S. aureus strain were investigated. Of the fatty acids tested, three C18 unsaturated fatty acids, that is, petroselinic, vaccenic, and oleic acids at 100 μg/mL, inhibited S. aureus biofilm formation by more than 65% without affecting its planktonic cell growth (MICs were all > 400 μg/mL). Notably, petroselinic acid significantly inhibited biofilm formation of two methicillin-resistant S. aureus strains and two methicillin-sensitive S. aureus strains. In addition, petroselinic acid significantly suppressed the production of three virulence factors, namely, staphyloxanthin, lipase, and α-hemolysin. Transcriptional analysis showed that petroselinic acid repressed the gene expressions of quorum sensing regulator agrA, effector of quorum sensing RNAIII, α-hemolysin hla, nucleases nuc1 and nuc2, and the virulence regulator saeR. Furthermore, petroselinic acid dose-dependently inhibited S. aureus biofilm formation on abiotic surfaces and porcine skin. These findings suggest that fatty acids, particularly petroselinic acid, are potentially useful for controlling biofilm formation by S. aureus. IMPORTANCE Fatty acids with a long carbon chain have recently attracted attention because of their antibiofilm activities against microbes. Here, we report the antibiofilm activities of 27 fatty acids against S. aureus. Of the fatty acids tested, three C18 unsaturated fatty acids (petroselinic, vaccenic, and oleic acids) significantly inhibited biofilm formation by S. aureus. Furthermore, petroselinic acid inhibited the production of several virulence factors in S. aureus. The study also reveals that the action mechanism of petroselinic acid involves repression of quorum-sensing-related and virulence regulator genes. These findings show that natural and nontoxic petroselinic acid has potential use as a treatment for S. aureus infections, including infections by methicillin-resistant S. aureus strains, and in food processing facilities.