Genetic alterations responsible for reduced susceptibility to vancomycin in community-associated MRSA strains of ST72.
J Antimicrob Chemother
; 72(9): 2454-2460, 2017 09 01.
Article
em En
| MEDLINE
| ID: mdl-28595277
ABSTRACT
Objectives:
We previously reported the first case of vancomycin treatment failure due to development of vancomycin-intermediate resistance in a patient with an MRSA of ST72, a community genotype in Korea. We investigated two isogenic MRSA strains from this patient, who experienced treatment failure with vancomycin and rifampicin.Methods:
We tracked the genetic alterations that confer reduced susceptibility to vancomycin on those two isogenic MRSA strains by WGS.Results:
Five non-synonymous mutations were identified, including rpoB (H481Y), dprA (G196C), femA (F92C), vraR (E127K) and agrC (E391stop). We further studied the role of a mutation of vraR in reduced susceptibility to vancomycin. Introduction of the mutated vraR (E127K) into a vancomycin-susceptible Staphylococcus aureus strain resulted in an increase in vraSR mRNA expression and vancomycin MIC and development of the hetero-VISA phenotype, which was confirmed by the population analysis profile (PAP)/AUC. Electron microscopy showed increased cell wall thickness in the strains with mutated vraR.Conclusions:
Based on the genomic data, molecular experiments and PAP and cell wall analyses, we propose that a single mutation of vraR is associated with the reduced susceptibility to vancomycin in MRSA and further treatment failure.
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Base de dados:
MEDLINE
Assunto principal:
Infecções Estafilocócicas
/
Vancomicina
/
Infecções Comunitárias Adquiridas
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Staphylococcus aureus Resistente à Meticilina
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Antibacterianos
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article