Antibiotic-Resistant Staphylococcus aureus Does Not Develop Resistance to Vanillic Acid and 2-Hydroxycinnamic Acid after Continuous Exposure in Vitro

[Image: see text] Development of resistance to antibiotics is one of the major reasons of difficulties in treatments of diseases caused by antibiotic-resistant bacteria, and this resistance makes the investigation of alternative antimicrobials a key priority. Phenolic acids are plant- and fungi-originating natural antimicrobial products, and there is no known bacterial resistance after exposure to them. The purpose of this study was to investigate the resistance ability of bacteria against phenolic acids. Therefore, the ability of methicillin-resistant Staphylococcus aureus and methicillin-susceptible S. aureus to gain resistance against two phenolic acids and an antibiotic upon exposure to subinhibitory concentrations was tested. Herein, we evaluated the minimum inhibitory concentrations (MICs) of vanillic acid (VA), 2-hydroxycinnamic acid (2-HCA), and vancomycin in the beginning of the experiment and the MICs were found to be 2.5 mg/mL VA, 1.6 mg/mL 2-HCA, and 0.01 mg/mL vancomycin for both bacteria. Following continuous treatments with increasing subinhibitory concentrations, MICs were evaluated once more. Exposure to subinhibitory concentrations of vancomycin induced the development of resistance immediately; however, resistance to both phenolic acids could not be induced. These data indicated the potential of phenolic acids to be used as effective antimicrobials in the inhibition of antibiotic-resistant pathogenic bacteria.