title: Reversal of ampicillin resistance in MRSA via inhibition of penicillin-binding protein 2a by Acalypha wilkesiana.
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.
authors.affiliation: Faculty of Science, University of Nottingham Malaysia Campus, Jalan Broga, 43500 Semenyih, Selangor, Malaysia.
authors.forename: Carolina
authors.identifier: 0000-0002-2876-5131
authors.initials: C
authors.lastname: Santiago
authors.affiliation: Faculty of Science, University of Nottingham Malaysia Campus, Jalan Broga, 43500 Semenyih, Selangor, Malaysia.
authors.forename: Ee Leen
authors.identifier: 0000-0003-0804-1782
authors.initials: EL
authors.lastname: Pang
authors.affiliation: Faculty of Science, University of Nottingham Malaysia Campus, Jalan Broga, 43500 Semenyih, Selangor, Malaysia.
authors.forename: Kuan-Hon
authors.initials: KH
authors.lastname: Lim
authors.affiliation: Faculty of Science, University of Nottingham Malaysia Campus, Jalan Broga, 43500 Semenyih, Selangor, Malaysia.
authors.forename: Hwei-San
authors.identifier: 0000-0002-6173-6367
authors.initials: HS
authors.lastname: Loh
authors.affiliation: Faculty of Science, University of Nottingham Malaysia Campus, Jalan Broga, 43500 Semenyih, Selangor, Malaysia.
authors.forename: Kang Nee
authors.identifier: 0000-0002-7818-3922
authors.initials: KN
authors.lastname: Ting
mesh_terms: D065815:Acalypha / Q000737:chemistry; D000667:Ampicillin / Q000008:administration & dosage*; D000668:Ampicillin Resistance / Q000187:drug effects; D004357:Drug Synergism; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics; D046915:Penicillin-Binding Proteins / Q000096:biosynthesis; D010453:Peptide Synthases / Q000096:biosynthesis; D010936:Plant Extracts / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D046915:Penicillin-Binding Proteins; D010936:Plant Extracts; C478699:penicillin-binding protein 2a, Streptococcus; D000667:Ampicillin; D010453:Peptide Synthases
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