Abstract
We previously reported a negative correlation between vancomycin and linezolid susceptibility in Staphylococcus aureus (S. aureus) (Watanabe Y, et al : Antimicrob Agents Chemother, 2008; 52 : 4207-4208). In the present study, we evaluated changes in the correlations of susceptibility of vancomycin-intermediate S. aureus (VISA) to linezolid and vancomycin with the mutations of rpoB, vraSR, graRS, clpP and walRK. These mutations have been proven to contribute to the decreased vancomycin susceptibility of VISA. Of 40 VISA strains, 29 (72.5%), 9 (22.5%), 4 (10%), 3 (7.5%) and 23 (57.5%) strains carried mutation in rpoB, vraSR, graRS, clpP and walRK, respectively. Statistical analysis showed that the level of improvement in linezolid susceptibility was significant only for the rpoB mutation group. Population analysis for hVISA Mu3 and its graR - and/or rpoB -mutated mutants showed that the rpoB mutation significantly increased linezolid susceptibility, while the graR mutation significantly reduced vancomycin susceptibility. Interestingly, MIC determination with 41 rifampicin- and 46 vancomycin-selected mutants generated from 7 clinical MRSA strains showed that the MIC of linezolid was reduced by 0.45 ± 0.25 for rifampicin-selected mutants and by 0.24 ± 0.28 mg/l for vancomycin-selected mutants. For the vancomycin MIC, the rifampicin-selected mutants increased by 0.40 ± 0.37, while the vancomycin-selected mutants increased by 1.21 ± 0.74 mg/l, when compared to the parent strains. Moreover, a study with 20 rpoB -mutants developed by exposing N315Δ IP in vitro to rifampicin showed that all mutants had improved linezolid susceptibility, but this was not accompanied by a change in vancomycin susceptibility in 19 of 20 mutants. Taken together, we conclude that rpoB mutation may play a contributory role in the improvement of linezolid susceptibility in S. aureus.
