Reversal of Ampicillin Resistance in MRSA via Inhibition of Penicillin-Binding Protein 2a by Acalypha wilkesiana

• Published in: BioMed research international Vol. 2014; no. 2014; pp. 1 - 7
• Main Authors: Santiago, Carolina, Pang, Ee Leen, Lim, Kuan-Hon, Loh, Hwei-San, Ting, Kang Nee
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Puplishing Corporation 01-01-2014; Hindawi Publishing Corporation; John Wiley & Sons, Inc; Hindawi Limited
• Subjects: Acalypha; Acalypha - chemistry; Ampicillin; Ampicillin - administration & dosage; Ampicillin Resistance - drug effects; Antibiotics; Bacteriology; Care and treatment; Colleges & universities; Drug resistance in microorganisms; Drug Synergism; Euphorbiaceae; Gene Expression Regulation, Bacterial - drug effects; Health aspects; Medicinal plants; Metabolites; Methicillin-Resistant Staphylococcus aureus - drug effects; Methicillin-Resistant Staphylococcus aureus - genetics; Penicillin; Penicillin-Binding Proteins - biosynthesis; Peptide Synthases - biosynthesis; Physiological aspects; Plant Extracts - administration & dosage; Plant Extracts - chemistry; Protein binding; Proteins; Solvents; Staphylococcus aureus; Staphylococcus aureus infections; Staphylococcus infections; Tropical diseases; Selangor Malaysia
• ISSN: 2314-6133; 2314-6141
• DOI: 10.1155/2014/965348

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.