Journal article

Evolution of multidrug resistance during staphylococcus aureus infection involves mutation of the essential two component regulator WalKR

BP Howden, CRE McEvoy, DL Allen, K Chua, W Gao, PF Harrison, J Bell, G Coombs, V Bennett-Wood, JL Porter, R Robins-Browne, JK Davies, T Seemann, TP Stinear

Plos Pathogens | Published : 2011

Open access

Abstract

Antimicrobial resistance in Staphylococcus aureus is a major public health threat, compounded by emergence of strains with resistance to vancomycin and daptomycin, both last line antimicrobials. Here we have performed high throughput DNA sequencing and comparative genomics for five clinical pairs of vancomycin-susceptible (VSSA) and vancomycin-intermediate ST239 S. aureus (VISA); each pair isolated before and after vancomycin treatment failure. These comparisons revealed a frequent pattern of mutation among the VISA strains within the essential walKR two-component regulatory locus involved in control of cell wall metabolism. We then conducted bi-directional allelic exchange experiments in ou..

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