Abstract
The inhibitory activity of a semipure fraction from the plant, Acalypha wilkesiana assigned as 9EA-FC-B, alone and in combination with ampicillin, was studied against methicillin-resistant Staphylococcus aureus (MRSA). In addition, effects of the combination treatment on PBP2a expression were investigated. Microdilution assay was used to determine the minimal inhibitory concentrations (MIC). Synergistic effects of 9EA-FC-B with ampicillin were determined using the fractional inhibitory concentration (FIC) index and kinetic growth curve assay. Western blot experiments were carried out to study the PBP2a expression in treated MRSA cultures. The results showed a synergistic effect between ampicillin and 9EA-FC-B treatment with the lowest FIC index of 0.19 (synergism ≤ 0.5). The presence of 9EA-FC-B reduced the MIC of ampicillin from 50 to 1.56 μg mL−1. When ampicillin and 9EA-FC-B were combined at subinhibitory level, the kinetic growth curves were suppressed. The antibacterial effect of 9EA-FC-B and ampicillin was shown to be synergistic. The synergism is due the ability of 9EA-FC-B to suppress the activity of PBP2a, thus restoring the susceptibility of MRSA to ampicillin. Corilagin was postulated to be the constituent responsible for the synergistic activity showed by 9EA-FC-B.
Highlights
Infection caused by methicillin-resistance Staphylococcus aureus (MRSA) is a world-wide health problem
The minimal inhibitory concentrations (MIC) value of ampicillin against MRSA notably confirmed the resistance of the studied strain, while MIC value of ampicillin against MSSA revealed the susceptibility of this strain to the antibiotic
The anti-MRSA activity of fraction 9EA-FC-B was fourfold more effective than crude extract 9EA
Summary
Infection caused by methicillin-resistance Staphylococcus aureus (MRSA) is a world-wide health problem. PBP2a, in turn, replaces the function of normal PBPs (blocked by beta-lactams) in the resistant strains for cell wall biosynthesis [4]. This confers MRSA resistance to the entire beta-lactam family. It has been observed that extracts, fractions, or metabolites of plant origin are able to inhibit production of PBP2a when they are used in combination with current available antibiotics. In a review article [6], combinations of drugs such as beta-lactams and beta-lactamase inhibitors of plant origin have been shown to exhibit synergistic activities against antibiotic resistant microorganisms. In continuation to our earlier findings, we have embarked to further investigate the effects of the semipure extracts of A. wilkesiana in the reversal of ampicillin resistance in MRSA
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