Mutations in rpoB and fusA cause resistance to rifampicin and fusidic acid in methicillin-resistant Staphylococcus aureus strains from a tertiary hospital in Malaysia

• Main Authors: Lim, K.T., Teh, C.S.J., Mohd Yasim, M.Y., Thong, Kwai Lin
• Format: Article
• Language: English; English
• Published: Oxford University Press 2013
• Subjects: QR Microbiology
• Online Access: http://eprints.um.edu.my/10649/1/Lim%2C_2013.pdf; http://eprints.um.edu.my/10649/2/Lim%2C_2013.pdf; http://eprints.um.edu.my/10649/; https://doi.org/10.1093/trstmh/trt111
• Institution: Universiti Malaya

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.