Novel adjuvant strategy to potentiate bacitracin against MDR MRSA

Objectives: Bacitracin is an antimicrobial peptide that is frequently used as an active ingredient in antimicrobial ointments. However, bacitracin resistance is highly prevalent in community-associated MRSA (CA-MRSA) strains and significantly compromises the effectiveness of existing antimicrobial ointments. In this study, we aimed to develop novel adjuvants to enhance the antimicrobial activity of bacitracin by using alkyl gallates. Methods: The growth of MRSA USA300, the predominant CA-MRSA strain in the USA, was determined in the presence of bacitracin and alkyl gallates at various concentrations. The viability of USA300 and MDR clinical isolates of MRSA was measured after exposure to various combinations of bacitracin and alkyl gallates. Results: Whereas 100 U/mL bacitracin did not inhibit USA300, 1 U/mL bacitracin in combination with as low as 2 mg/L octyl gallate (OG) and 8 mg/L dodecyl gallate (DG), respectively, completely inhibited the growth of USA300. Among the tested alkyl gallates, OG most significantly enhanced the bactericidal activity of bacitracin. For example, 10^-3 U/mL bacitracin with 5 mg/L OG effectively killed USA300, which is an 200000-fold decrease in the MBC of bacitracin for USA300. Furthermore, bacitracin/OG combinations demonstrated similar levels of antimicrobial activity against human clinical isolates of MRSA resistant to multiple antibiotics of clinical importance. Conclusions: Some alkyl gallates, particularly OG, significantly increased the antimicrobial activity of bacitracin against MDR MRSA.