Molecular epidemiology and mechanism of resistance of invasive quinolone-resistant South African isolates of Salmonella enterica, 2004-2006

Govender, Nevashan
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The molecular epidemiology and mechanism of quinolone resistance of South African human isolates of Salmonella Typhi for the period 2003-2007, Salmonella Enteritidis, Salmonella Isangi and Salmonella Typhimurium for the period 2004-2006, received by the Enteric Diseases Reference Unit (EDRU) of the National Institute for Communicable Diseases was investigated. Molecular epidemiology was investigated using pulsed-field gel electrophoresis (PFGE) analysis for all four serotypes, as well as multiple-locus variable-number tandem-repeats analysis (MLVA) for Salmonella Typhi and Salmonella Typhimurium. Three probable mechanisms for quinolone resistance were investigated which included: amino acid mutations in the quinolone resistance determining regions (QRDRs) of DNA gyrase (gyrA/gyrB) and topoisomerase IV (parC/parE), active efflux of antibiotic out the bacterial cell and plasmid-mediated resistance encoded by qnr genes. For the period 2003-2007, 498 human isolates of Salmonella Typhi were received by the EDRU, of which 27 were resistant to nalidixic acid (MICs, ≥32 μg/ml). Only 19 Salmonella Typhi quinolone-resistant isolates were available for analysis. For the period 2004-2006, 329 human isolates of Salmonella Enteritidis, 1005 human isolates of Salmonella Isangi and 2624 human isolates of Salmonella Typhimurium were received by the EDRU. Of these isolates, 119 Salmonella Enteritidis, 143 Salmonella Isangi and 532 Salmonella Typhimurium were invasive, nalidixic acid-resistant. Only 116 Salmonella Enteritidis, 137 Salmonella Isangi and 516 Salmonella Typhimurium invasive, nalidixic acid-resistant isolates were available for analysis. For each respective serotype the isolates were genetically diverse as they could be differentiated into many PFGE types, suggesting that quinolone-resistant strains have emerged independently of one another for all four serotypes. The use of MLVA for Salmonella Typhi and Salmonella Typhimurium also illustrated the genetic diversity of the isolates by differentiating the isolates in various MLVA types. The investigation into the contributory mechanisms of resistance showed that an over-active efflux system in combination with mutations in both gyrA and parC play a major role in facilitating quinolone resistance in Salmonella Typhi, Salmonella Enteritidis and Salmonella Isangi. These very same mechanisms were also found to be responsible for the quinolone resistance in the majority of the Salmonella Typhimurium isolates along with the rarely isolated mechanism of resistance, a qnr plasmid. This is the first report of any kind identifying the presence of qnr genes in South African Enterobacteriaceae isolates. Our study also highlights the need for further work to establish the link amongst the various mechanisms of resistance as their interactions remains unclear.