title: Mutations in rpoB and fusA cause resistance to rifampicin and fusidic acid in methicillin-resistant Staphylococcus aureus strains from a tertiary hospital in Malaysia.
abstract: BACKGROUND
  The prevalence of resistance to rifampicin and fusidic acid among Malaysian strains of methicillin-resistant Staphylococcus aureus (MRSA) is increasing. This study aimed to determine the mechanisms of rifampicin and fusidic acid resistance and the genetic diversity of MRSA strains from a Malaysian tertiary hospital.
  
  
  METHODS
  Minimum inhibitory concentrations (MIC) for 21 MRSA strains were determined by agar dilution test and Etest. The resistance genes, staphylococcal chromosome cassette mec (SCCmec) types, multilocus-sequence typing (MLST) types and spa types, were determined by PCR and DNA sequencing.
  
  
  RESULTS
  MIC for rifampicin and fusidic acid resistance ranged from <1 to 8 µg/ml and from <1 to 256 µg/ml, respectively. A double mutation (484Arg/His and 517Glu/Gln) in rpoB causes high rifampicin resistance while a mutational change (461Leu/Lys) in fusA was observed in seven strains highly resistant to fusidic acid. Five of the seven were also resistant to rifampicin (MIC 8 µg/ml) and carried a mutated rpoB gene (484Arg/His). No other acquired fusidic acid resistance gene (fusB, fusC or fusD) was detected. Most (14/21) of the strains belonged to clone ST239-III-t037. Three belonged to ST22-IV-t1378 and the remaining four to ST239-III-t2029, ST239-III-t421, ST1178-IV-t1107 and ST241-III-t363, respectively.
  
  
  CONCLUSIONS
  The study showed that both rifampicin and fusidic acid resistance was associated with mutational change in rpoB and fusA, respectively. All rifampicin-resistant strains were from the same clone ST239-III-t037 whereas strains resistant to fusidic acid were genetically more diverse.
authors: Institute of Biological Science, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors: King-Ting
authors: KT
authors: Lim
authors: Cindy Shuan Ju
authors: CS
authors: Teh
authors: Mohd Yasim Mohd
authors: MY
authors: Yusof
authors: Kwai-Lin
authors: KL
authors: Thong
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics*; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D005672:Fusidic Acid / Q000494:pharmacology*; D008296:Malaysia / Q000453:epidemiology; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects / Q000235:genetics*; D008826:Microbial Sensitivity Tests; D020653:Peptide Elongation Factor G / Q000235:genetics*; D012293:Rifampin / Q000494:pharmacology*; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; C492444:FusA protein, Staphylococcus aureus; D020653:Peptide Elongation Factor G; D005672:Fusidic Acid; D012293:Rifampin
keywords: MLST; Staphylococcus aureus; mutation; rifampicin fusidic acid; spa