aureus strains. The mutations found in clinical strains are described under the scheme of the rpoB gene, and those generated in the laboratory are described above the scheme. All of the rifampicin-resistant VISA clinical strains possessed mutations within the rifampicin resistance-determining region (RRDR).

C59 wnt manufacturer Six strains were rifampicin-susceptible VISA strains (MIC < 1 mg/L) whose mutations were found outside of the RRDR of the rpoB gene ( Table 1 and Fig. 5). Such strains having mutation outside the RRDR can be easily obtained in vitro from hVISA strain Mu3 by selection with vancomycin, but not with rifampicin. Such strains tend to have higher levels of vancomycin resistance than those selected by rifampicin [34]. For example, laboratory-derived mutant strains with rpoB(T480M), rpoB(R503H) and rpoB(S746Y) possessed vancomycin MICs of 7, 9 and 9 mg/L, respectively. These values were significantly higher than 4–5 mg/L of the mutants with rpoB(H481Y) and other RRDR mutations [34].rpoB mutations affect susceptibility of not only rifampicin and vancomycin but also of other categories of antibiotics. Depending on the location and kinds of amino acid substitution, rpoB mutations cause a variety of phenotypic

changes. Especially notable are susceptibilities ABT-199 ic50 to vancomycin, daptomycin and linezolid ( Fig. 5). Daptomycin and vancomycin MICs are positively correlated [32], [40], [41] and [52]. In Mu50, graR(N197S) mutation appears to have raised daptomycin resistance by increasing the positive charge of the cell surface through enhanced expression of the mprF gene [32] and [35]. rpoB-mediated dual resistance to vancomycin

and daptomycin was first demonstrated in laboratory strain ΔIP-10*3d1 that acquired reduced susceptibility to both antibiotics after serial daptomycin selection. A single mutation, rpoB(A621E), was responsible for the dual resistance phenotype [52]. This indicated that PIK3C2G multiple cellular phenotypes separately controlled by independent regulators may be altered by a single rpoB mutation. We also noticed a negative correlation between vancomycin MICs and linezolid MICs among clinical VISA strains [60]. Now we found that certain rpoB mutations represented by rpoB(S746F) increase linezolid susceptibility and decrease vancomycin susceptibility at the same time [34]. Some rpoB mutations also have a profound influence on methicillin resistance [61]. Expression of the methicillin resistance gene mecA is not enough for S. aureus cells to express high-level methicillin resistance (defined as an MIC > 128 mg/L for oxacillin or >4 mg/L for imipenem). Acquisition of certain chromosomal mutations (chr*) was known to be required to convert the mecA-carrying S. aureus into highly methicillin-resistant S. aureus or homogeneously methicillin-resistant S. aureus (homo-MRSA). Without chr*, S. aureus stays as heterogeneously methicillin-resistant S. aureus (hetero-MRSA).