title: In vitro profiling of antimethicillin-resistant Staphylococcus aureus activity of thymoquinone against selected type and clinical strains.
abstract: This study explores antimethicillin-resistant Staphylococcus aureus (MRSA) activity of a bioactive phytochemical constituent, thymoquinone obtained from the medicinal herb, Nigella sativa Linn. Based on initial assessment on crude extract of seeds of Nigella sativa Linn, the pure active constituent was employed in the study. A total of 99 MRSA strains which comprised of 40 types and 59 clinical strains were selected for the study. Minimum inhibitory concentration (MIC), bactericidal activity, postantibiotic effect (PAE) and propensity to select resistant mutants were determined using standard protocols. Results revealed that thymoquinone exhibited MIC in the range of 8-16 μg ml(-1) and MIC90 of 16 μg ml(-1) against MRSA strains. It was bactericidal to MRSA by demonstrating >3 log kill. It showed a longer PAE of 3·2 ± 0·2 h. Upon exposure to high-density inoculum of MRSA, it did not select resistant mutants. Transmission electron microscopy of thymoquinone-treated MRSA showed no lysis but damage to cell wall and cell membrane which corroborated well with the salt tolerance and bacteriolysis assays. In conclusion, MIC90 , bactericidal property, longer PAE, absence of resistant mutant selection and damages in cell membrane and cell wall imply a promising anti-MRSA activity of thymoquinone.
  
  
  CONCLUSIONS
  This is the first detailed report on anti-MRSA activity of thymoquinone. The assessment was made with both type and clinical strains. Thymoquinone may be a potential lead compound which can be further optimized to discover novel anti-MRSA agents.
authors.affiliation: Orchid Chemicals and Pharmaceuticals Ltd., Chennai, India.
authors.forename: P
authors.initials: P
authors.lastname: Hariharan
authors.affiliation: Orchid Chemicals and Pharmaceuticals Ltd., Chennai, India.
authors.forename: M
authors.initials: M
authors.lastname: Paul-Satyaseela
authors.affiliation: Microbiology Division, CSIR-CLRI, Chennai, India.
authors.forename: A
authors.initials: A
authors.lastname: Gnanamani
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D016227:Benzoquinones / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects; D002473:Cell Wall / Q000187:drug effects; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D046529:Microscopy, Electron, Transmission; D010936:Plant Extracts / Q000494:pharmacology; D013203:Staphylococcal Infections / Q000188:drug therapy
chemical_list: D000900:Anti-Bacterial Agents; D016227:Benzoquinones; D010936:Plant Extracts; C003466:thymoquinone
keywords: MRSA; Nigella sativa Linn; antibacterial; phytochemical; thymoquinone