However, it seems VRT752271 in vivo more likely that RN4220 contains the SNP (GCT → GCG), which arose once in this strain. This can only be confirmed when more rpoB sequences of S. aureus isolates from a variety of genetic backgrounds become available. Of greater interest is the only other conserved silent SNP found in the codon for arginine at amino acid position

512 (CGT → CGC) that was observed in all ST612-MRSA-IV isolates (Table 2). This mutation was notable for two reasons: firstly, AT-rich organisms such as S. aureus more commonly favour AT-rich codons with either adenine or thymine bases, rather than cytosine, at the third https://www.selleckchem.com/products/lazertinib-yh25448-gns-1480.html position [21, 22]; secondly, codon usage tables indicated Selleck PX-478 that CGT is more common than CGC for arginine [20]. Thus, it is possible to suggest that the SNP (CGT → CGC) has not arisen on multiple occasions in ST612-MRSA-IV, but instead was inherited from a common ancestor and has been conserved within the lineage. Interestingly, ST612-MRSA-IV has also recently been reported as the predominant clone in a population of horses in Australia [23]. All of the equine ST612-MRSA-IV isolates that were tested were rifampicin-resistant, making it tempting to speculate that they may be related to those described in this study; however,

the equine strains carried SCCmec type IVa [23], while the ST612-MRSA-IV isolates from Cape Town and Australia carried SCCmec type lished data), which suggests at least two separate SCCmec acquisitions in this genetic background. Although mutations associated with resistance frequently evince an initial fitness

cost to the organism, it has been shown that rifampicin-resistant E. coli do not revert to wild-type susceptibility in the absence of this antibiotic. Rather, they persist because of their capacity to develop compensatory mutations, which restore bacterial fitness [24]. Other studies have also suggested that the reduction of antibiotic pressure may not necessarily result in reversion to susceptibility [25], which is worrying in our setting given that until ST612-MRSA-IV is multidrug-resistant [5]. Vancomycin remains the drug of choice for the treatment of multidrug-resistant MRSA infections; however, the emergence of vancomycin-resistant S. aureus poses a new challenge. Watanabe et al. [17] have suggested that certain mutational changes in rpoB, including H481Y, may be linked to reduced vancomycin susceptibility in S. aureus. In light of these facts, the vancomycin MICs of isolates selected for rpoB genotyping in the current study were determined by E-test. Interestingly, the ST5-MRSA-I isolate, with rpoB genotype H481Y, was susceptible to vancomycin (MIC of 2 mg/L). Of interest is the observation that isolates with MICs of 2 mg/L have been associated with a poor clinical response to vancomycin [26].