title: Piperine as an inhibitor of the MdeA efflux pump of Staphylococcus aureus.
abstract: Piperine, a trans-trans-isomer of 1-piperoyl-piperidine, was tested in combination with mupirocin for antimicrobial activity against Staphylococcus aureus strains including meticillin-resistant S. aureus. The combination markedly reduced the MIC of mupirocin and also lowered the mutation frequency. Enhanced accumulation and efflux of ethidium bromide from wild-type and mutant (Mup(r)-1) strains in the presence of piperine indicated that inhibition of efflux could be a possible mechanism of potentiation of mupirocin activity by piperine. The combination of piperine with mupirocin in a dermal infection model of mice showed better in vivo efficacy when compared with the commercially available formulation of 2 % mupirocin.
authors.affiliation: Department of Biochemistry, Faculty of Science, University of Kashmir, Hazartbal, Srinagar 190 001, India.
authors.forename: Zahid Mehmood
authors.initials: ZM
authors.lastname: Mirza
authors.affiliation: Clinical Microbiology Division, Indian Institute of Integrative Medicine, Canal Road, Jammu Tawi 180 001, India.
authors.forename: Ashwani
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Clinical Microbiology Division, Indian Institute of Integrative Medicine, Canal Road, Jammu Tawi 180 001, India.
authors.forename: Nitin Pal
authors.initials: NP
authors.lastname: Kalia
authors.affiliation: Department of Biochemistry, Faculty of Science, University of Kashmir, Hazartbal, Srinagar 190 001, India.
authors.forename: Afzal
authors.initials: A
authors.lastname: Zargar
authors.affiliation: Clinical Microbiology Division, Indian Institute of Integrative Medicine, Canal Road, Jammu Tawi 180 001, India.
authors.forename: Inshad Ali
authors.initials: IA
authors.lastname: Khan
mesh_terms: D000470:Alkaloids / Q000378:metabolism* / Q000627:therapeutic use; D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism* / Q000627:therapeutic use; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors*; D052117:Benzodioxoles / Q000378:metabolism* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000378:metabolism* / Q000627:therapeutic use; D004996:Ethidium / Q000378:metabolism; D005260:Female; D026901:Membrane Transport Proteins; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000201:enzymology*; D051379:Mice; D008826:Microbial Sensitivity Tests; D016712:Mupirocin / Q000378:metabolism; D010880:Piperidines / Q000378:metabolism* / Q000627:therapeutic use; D053284:Polyunsaturated Alkamides / Q000378:metabolism* / Q000627:therapeutic use; D012376:Rodent Diseases / Q000188:drug therapy; D013203:Staphylococcal Infections / Q000188:drug therapy; D016896:Treatment Outcome
chemical_list: D000470:Alkaloids; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D052117:Benzodioxoles; D004791:Enzyme Inhibitors; C510398:MdeA protein, Staphylococcus aureus; D026901:Membrane Transport Proteins; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D016712:Mupirocin; D004996:Ethidium; C008922:piperine