Antibacterial Activity of Exogenous Glutathione and Its Synergism on Antibiotics in Methicillin-Associated Multidrug Resistant Clinical Isolates of Staphylococcus aureus

摘要

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most problematic human pathogens. Antibiotic treatment of MRSA often associated with resistance to multiple classes of antibiotics is extremely challenging and urgently demands action to treat MRSA. Glutathione (GSH) is a biogenic thiol-compound that maintains an optimal intracellular redox-potential required for various normal cellular processes. Antibacterial activity of exogenous GSH has been reported in some bacterial pathogens but is largely unknown in MRSA. Aim: This study aimed to understand antibacterial activity of GSH, its role in antibiotic susceptibility, and a potential antibacterial mechanism in clinical isolates of S. aureus. Materials and Methods: Minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), checkerboard, time-killing, and bacterial killing assays were performed for 14 clinical isolates of S. aureus including 10 MRSA and two type strains (ATCC 700699 and 35556). Results: MIC and MBC levels for the clinical and type strains were 15 - 20 mM and 25 - 40 mM of GSH, respectively. Subinhibitory concentrations of GSH synergistically enhanced susceptibility of all tested-antibiotics, resulting in sensitizing all-tested S. aureus. Bacterial-killing produced by GSH-mediated acidity was significantly higher than that by hydrochloric acid-mediated acidity. Conclusion: Overall results concluded that GSH exhibited antibacterial activity on S. aureus regardless of antibiotic susceptibility and synergistically enhanced antibiotic susceptibility. Additionally, GSH-mediated acidity was one of the antibacterial mechanisms. These findings suggest that GSH may be a potential antimicrobial agent or adjuvant for the conventional anti-MRSA regimens.