RESUMO
Reduced vancomycin susceptibility in Staphylococcus aureus continues to trouble clinical microbiologists and infectious disease specialists. In this study, a vancomycin-susceptible S. aureus (VSSA) strain, which was methicillin-resistant (MRSA), was grown with and without subinhibitory levels of vancomycin, and the transcriptional profiles were determined by microarray analysis. Thirty-six genes were upregulated and 42 genes were down-regulated by more than two-fold (P< or =0.05) in the presence of vancomycin. Many of these genes are involved in cell-wall biosynthesis and regulation, but of particular interest was the upregulation of genes in the locus responsible for capsule synthesis. Increased capsule production following exposure of MRSA to low levels of vancomycin could explain treatment failure. This suggests that selected genes of the capsule locus could be used as diagnostic targets for monitoring patients undergoing treatment with vancomycin therapy, as an increase in their expression may indicate progressive development of low-level resistance.
Assuntos
Cápsulas Bacterianas/efeitos dos fármacos , Proteínas de Bactérias/genética , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Vancomicina/farmacologia , Antibacterianos/farmacologia , Humanos , Staphylococcus aureus Resistente à Meticilina/genética , Testes de Sensibilidade Microbiana/métodos , Análise de Sequência com Séries de OligonucleotídeosAssuntos
DNA/sangue , DNA/isolamento & purificação , Staphylococcus aureus Resistente à Meticilina/genética , Técnicas de Diagnóstico Molecular/métodos , Infecções Estafilocócicas/diagnóstico , Antibacterianos/farmacologia , Humanos , Meticilina/farmacologia , Resistência a Meticilina/genética , Testes de Sensibilidade Microbiana , Reação em Cadeia da Polimerase/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Infecções Estafilocócicas/microbiologiaRESUMO
This study examines the ability of isolates representing the 17 epidemic methicillin-resistant strains of Staphylococcus aureus to grow in increasing levels of vancomycin. Only EMRSAs 1, 2, 8, 11, 12 and 15 showed any growth and were designated EMRSAs 1A, 2A, 8A, 11A, 12A and 15A. On population analysis, these strains all produced clones that grew on 32 microg/mL vancomycin, while EMRSA 12A and 15A grew at 128 microg/mL. This was associated with increased resistance to lysostaphin and teicoplanin, a loss of phage sensitivity and an increase in cell wall diameter. Typing by pulsed-field gel electrophoresis following SmaI digestion showed no change in EMRSA 8A and 15A, while the other EMRSAs all lost or gained at least one band. EMRSAs 1A, 2A and 15A became more resistant to methicillin, and EMRSAs 8A, 11A and 12A became less resistant to methicillin. These results suggest that more than one mechanism is responsible for this phenomenon.
Assuntos
Antibacterianos/farmacologia , Resistência a Meticilina , Staphylococcus aureus/crescimento & desenvolvimento , Resistência a Vancomicina , Vancomicina/farmacologia , Infecção Hospitalar , Surtos de Doenças , Relação Dose-Resposta a Droga , Eletroforese em Gel de Campo Pulsado , Humanos , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacosRESUMO
The presence of lactoferrin at the concentration found in cystic fibrosis (CF) sputum (0.9 g/L) reduced MICs and MBCs of doxycycline for Burkholderia cepacia and Pseudomonas aeruginosa strains. MICs for B. cepacia fell by 32- to 64-fold, from highly resistant to clinically achievable values. Rifampicin MICs for B. cepacia strains were reduced by lactoferrin and for some strains MBCs were reduced. These findings suggest new therapeutic approaches to infections and question the relevance of standard sensitivity tests for CF pathogens. Addition of lactoferrin to media for the routine sensitivity testing of CF isolates might give more relevant results.