Abstract
Stilbenoids have been considered as an alternative phytotherapeutic treatment against methicillin-resistant Staphylococcus aureus (MRSA) infection. The combined effect of ε-viniferin and johorenol A with the standard antibiotics, vancomycin and linezolid, was assessed against MRSA ATCC 33591 and HUKM clinical isolate. The minimum inhibitory concentration (MIC) value of the individual tested compounds and the fractional inhibitory concentration index (FICI) value of the combined agents were, respectively, determined using microbroth dilution test and microdilution checkerboard (MDC) method. Only synergistic outcome from checkerboard test will be substantiated for its rate of bacterial killing using time-kill assay. The MIC value of ε-viniferin against ATCC 33591 and johorenol A against both strains was 0.05 mg/mL whereas HUKM strain was susceptible to 0.1 mg/mL of ε-viniferin. MDC study showed that only combination between ε-viniferin and vancomycin was synergistic against ATCC 33591 (FICI 0.25) and HUKM (FICI 0.19). All the other combinations (ε-viniferin-linezolid, johorenol A-vancomycin, and johorenol A-linezolid) were either indifferent or additive against both strains. However, despite the FICI value showing synergistic effect for ε-viniferin-vancomycin, TKA analysis displayed antagonistic interaction with bacteriostatic action against both strains. As conclusion, ε-viniferin can be considered as a bacteriostatic stilbenoid as it antagonized the bactericidal activity of vancomycin. These findings therefore disputed previous report that ε-viniferin acted in synergism with vancomycin but revealed that it targets similar site in close proximity to vancomycin's action, possibly at the bacterial membrane protein. Hence, this combination has a huge potential to be further studied and developed as an alternative treatment in combating MRSA in future.
Highlights
Infection with Staphylococcus aureus is a major cause of serious hospital and community-acquired bacteremia worldwide and is associated with significant morbidity and mortality, especially when inappropriately treated [1]
From the microdilution checkerboard assay, only the combination between ε-viniferin and vancomycin was synergistic against ATCC 33591 and HUKM strains with fractional inhibitory concentration index (FICI) values of 0.25 and 0.19, respectively
Combination of εviniferin and linezolid displayed an indifference reaction against methicillin-resistant Staphylococcus aureus (MRSA) ATCC 33591 and HUKM strains with FICI values of greater than 1 but less than 4
Summary
Infection with Staphylococcus aureus is a major cause of serious hospital and community-acquired bacteremia worldwide and is associated with significant morbidity and mortality, especially when inappropriately treated [1]. Most of the MRSA strains are resistant to multiple classes of antibiotics and cannot be treated with conventional ßlactams, making glycopeptides (vancomycin or teicoplanin) the only therapeutic solution [3]. Emergence of MRSA strains with reduced susceptibility to glycopeptides has emphasized the need for new effective drugs [4]. New antistaphylococcal drugs such as linezolid, which is the first oxazolidinone antibiotic to be approved by the Food and Drug Administration (FDA), have developed and shown efficacy comparable to that of vancomycin for the treatment of pneumonia and soft tissue infections [5, 6]. Linezolid has not been routinely prescribed because of higher
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