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Teicoplanin resistance in Staphylococcus haemolyticus is associated with mutations in histidine kinases VraS and WalK
Authors:Vladimir Vimberg  Jorunn Pauline Cavanagh  Oldřich Benada  Olga Kofroňová  Erik Hjerde  Leona Zieglerová  Gabriela Balíková Novotná
Affiliation:1. Institute of Microbiology v. v. i., The Czech Academy of Sciences, Pr?myslová 595, Vestec 252 50, Czech Republic;2. Department of Pediatrics, University Hospital of North Norway, Sykehusvegen 38, Tromsø 9019, Norway;3. Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø 9037, Norway;4. Institute of Microbiology v. v. i., The Czech Academy of Sciences, Vídeňská 1083, Prague 142 20, Czech Republic;5. Department of Chemistry, Norstruct, UiT The Arctic University of Norway, Sykhusvegen 23, Tromsø 9019, Norway
Abstract:We investigated the genetic basis of glycopeptide resistance in laboratory-derived strains of S. haemolyticus with emphasis on differences between vancomycin and teicoplanin. The genomes of two stable teicoplanin-resistant laboratory mutants selected on vancomycin or teicoplanin were sequenced and compared to parental S. haemolyticus strain W2/124. Only the two non-synonymous mutations, VraS Q289K and WalK V550 L were identified. No other mutations or genome rearrangements were detected. Increased cell wall thickness, resistance to lysostaphin-induced lysis and adaptation of cell growth rates specifically to teicoplanin were phenotypes observed in a sequenced strain with the VraS Q289K mutation. Neither of the VraS Q289K and WalK V550 L mutations was present in the genomes of 121 S. haemolyticus clinical isolates. However, all but two of the teicoplanin resistant strains carried non-synonymous SNPs in vraSRTU and walKR-YycHIJ operons pointing to their importance for the glycopeptide resistance.
Keywords:Resistance  Vancomycin  Teicoplanin  Mutation
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