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Métodos Terapéuticos y Terapias MTCI
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1.
PLoS One ; 14(12): e0227009, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31887179

RESUMEN

Methicillin-resistant Staphylococcus aureus (MRSA) infection is an important clinical concern in patients, and is often associated with significant disease burden and metastatic infections. There is an increasing evidence of heterogeneous vancomycin-intermediate S. aureus (hVISA) associated treatment failure. In this study, we aim to understand the molecular mechanism of teicoplanin resistant MRSA (TR-MRSA) and hVISA. A total of 482 MRSA isolates were investigated for these phenotypes. Of the tested isolates, 1% were identified as TR-MRSA, and 12% identified as hVISA. A highly diverse amino acid substitution was observed in tcaRAB, vraSR, and graSR genes in TR-MRSA and hVISA strains. Interestingly, 65% of hVISA strains had a D148Q mutation in the graR gene. However, none of the markers were reliable in differentiating hVISA from TR-MRSA. Significant pbp2 upregulation was noted in three TR-MRSA strains, which had teicoplanin MICs of 16 or 32 µg/ml, whilst significant pbp4 downregulation was not noted in these strains. In our study, multiple mutations were identified in the candidate genes, suggesting a complex evolutionary pathway involved in the development of TR-MRSA and hVISA strains.


Asunto(s)
Antibacterianos/farmacología , Staphylococcus aureus Resistente a Meticilina/genética , Infecciones Estafilocócicas/tratamiento farmacológico , Teicoplanina/uso terapéutico , Resistencia a la Vancomicina/genética , Vancomicina/farmacología , Antibacterianos/uso terapéutico , Proteínas Bacterianas/genética , Análisis Mutacional de ADN , ADN Bacteriano/genética , ADN Bacteriano/aislamiento & purificación , Regulación hacia Abajo , Regulación Bacteriana de la Expresión Génica/efectos de los fármacos , Humanos , India , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Pruebas de Sensibilidad Microbiana , Mutación/efectos de los fármacos , Operón/efectos de los fármacos , Operón/genética , Proteínas de Unión a las Penicilinas/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Infecciones Estafilocócicas/microbiología , Teicoplanina/farmacología , Insuficiencia del Tratamiento , Regulación hacia Arriba , Vancomicina/uso terapéutico , Resistencia a la Vancomicina/efectos de los fármacos
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