Genetic basis of rifampicin resistance in methicillin-resistant Staphylococcus aureus suggests clonal expansion in hospitals in Cape Town, South Africa

Abstract

BackgroundSince 2001, several studies have reported high rifampicin resistance rates (45 - 100%) among methicillin-resistant Staphylococcus aureus (MRSA) isolates from South Africa. The authors previously characterised 100 MRSA isolates from hospitals in Cape Town, South Africa; forty-five percent of these isolates were rifampicin-resistant. The majority (44/45) corresponded to ST612-MRSA-IV, which is prevalent in South Africa, but has not been reported frequently elsewhere. The remaining rifampicin-resistant isolate corresponded to ST5-MRSA-I. The aim of this study was to investigate further the prevalence and genetic basis of rifampicin-resistance in MRSA isolates from hospitals in Cape Town.ResultsBetween July 2007 and June 2011, the prevalence of rifampicin-resistant MRSA in hospitals in Cape Town ranged from 39.7% to 46.4%. Based on the results of the aforementioned study, nine ST612-MRSA-IV isolates, the rifampicin-resistant ST5-MRSA-I isolate, and two rifampicin-susceptible MRSA isolates were investigated. Four previously described ST612-MRSA-IV isolates, including two each from South Africa and Australia, were also included.The ST5-MRSA-I isolate carried a single mutational change, H481Y, commonly associated with high-level rifampicin resistance. All ST612-MRSA-IV isolates carried an uncommon double amino acid substitution in RpoB, H481N, I527M, whilst one of the Australian ST612-MRSA-IV isolates carried an additional mutation within rpoB, representing a novel rpoB genotype: H481N, I527M, K579R. All ST612-MRSA-IV isolates also shared a unique silent single nucleotide polymorphism (SNP) within rpoB.ConclusionsThat local ST612-MRSA-IV isolates described here share an uncommon rpoB genotype and a unique silent SNP suggests this clone may have undergone clonal expansion in hospitals in Cape Town. Further, the data suggest that these isolates may be related to rifampicin-resistant ST612-MRSA-IV previously described in South Africa and Australia.

Rifampicin resistance among multi-resistant MRSA clinical isolates from Chennai, India, and their molecular characterization

“…Furthermore, the high-level rifampicin resistance of the isolate S. aureus KM05 might be explained by the previously reported rifampicin high-level resistance-associated amino acid substitution at site 481, one of the most common rifampicin resistance genotypes found herein, which had been reported previously in several laboratory mutants and clinical isolates (Jansen van Rensburg et al, 2012). This substitution leads to disruption of an H bond between rifampicin and RNA polymerase, and also reduces hydrophobic interactions within the binding cavity, thereby decreasing the affinity of the drug for its target (Jansen van Rensburg et al, 2012). To our knowledge, the amino acid substitutions in amino acid positions 455 and 529 have not been previously reported.…”

“…Genetic studies carried out to identify catalytically important amino acid changes affecting transcription termination in yeast RNA polymerase III showed that the mutations in regions of the RET1 gene encoding amino acids 455-486 are the termination-altering ones (Shaaban et al, 1995). Furthermore, the high-level rifampicin resistance of the isolate S. aureus KM05 might be explained by the previously reported rifampicin high-level resistance-associated amino acid substitution at site 481, one of the most common rifampicin resistance genotypes found herein, which had been reported previously in several laboratory mutants and clinical isolates (Jansen van Rensburg et al, 2012). This substitution leads to disruption of an H bond between rifampicin and RNA polymerase, and also reduces hydrophobic interactions within the binding cavity, thereby decreasing the affinity of the drug for its target (Jansen van Rensburg et al, 2012).…”

“…The majority of S. aureus rifampicin resistance mutations have been mapped to the conserved rifampicin resistance-determining region of the rpoB gene (Jansen van Rensburg et al, 2012). S. aureus rifampicin resistance is typically due to amino acid substitutions in the three known clusters (I, II, and III) of the RNA polymerase β-subunit rifampicin-binding site, and the point mutations in clusters I and II are identified as their genetic determinants.…”

MRSA in Africa: Filling the Global Map of Antimicrobial Resistance

“…Additionally, 3 more studies were retrieved from Google searches and 7 more studies were identified from hand-searching the bibliographic references of relevant studies. Finally, 32 studies were evaluated in this review [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41], [42], [43], [44], [45], [46], [47], [48], [49], [50], [51], [52], [53], [54], [55], [56], [57].…”

“…The prevalence of MRSA in this population was 39%. The most recent study from South Africa was retrospective in nature and referred to a period between 2007 and 2011 [55]. A large number of isolates, 13.746 in total, were collected from three tertiary- and two secondary-level public hospitals.…”