RESUMEN
The frequency of typical and atypical Beijing strains of Mycobacterium tuberculosis was determined in the Netherlands; Vietnam; and Hong Kong Special Administrative Region, People's Republic of China. The strains' associations with drug resistance, M. bovis BCG vaccination, and patient characteristics were assessed. BCG vaccination may have positively selected the prevalent typical Beijing strains.
Asunto(s)
Anticuerpos Antibacterianos/inmunología , Vacuna BCG/administración & dosificación , Farmacorresistencia Bacteriana , Mycobacterium tuberculosis , Tuberculosis/inmunología , Adulto , Variación Antigénica , Antituberculosos/farmacología , Vacuna BCG/inmunología , China , Elementos Transponibles de ADN , Femenino , Genotipo , Hong Kong , Humanos , Isoniazida/farmacología , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Mycobacterium tuberculosis/clasificación , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/inmunología , Mycobacterium tuberculosis/aislamiento & purificación , Países Bajos , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Factores de Riesgo , Tuberculosis/microbiología , Tuberculosis/prevención & control , Vacunación , VietnamRESUMEN
OBJECTIVES: To characterize 250 drug-resistant Mycobacterium tuberculosis (MTB) isolates in Hong Kong with respect to their drug susceptibility phenotypes to five common anti-tuberculosis drugs (ofloxacin, rifampicin, ethambutol, isoniazid and pyrazinamide) and the relationship between such phenotypes and the patterns of genetic mutations in the corresponding resistance genes (gyrA, rpoB, embB, katG, inhA, ahpC and pncA). METHODS: The MIC values of the aforementioned anti-tuberculosis drugs were determined for each of the 250 drug-resistant MTB clinical isolates by the absolute concentration method. Genetic mutations in the corresponding resistance genes in these MTB isolates were identified by PCR-single-stranded conformation polymorphism/multiplex PCR amplimer conformation analysis (SSCP/MPAC), followed by DNA sequencing of the purified PCR products. RESULTS: Resistance to four or five drugs was commonly observed in these MTB isolates; such phenotypes accounted for over 34% of the 250 isolates. The most frequently observed phenotypes were those involving both rifampicin and isoniazid, with or without additional resistance to the other drugs. A total of 102 novel mutations, which accounted for 80% of all mutation types detected in the 7 resistance genes, were recovered. Correlation between phenotypic and mutational data showed that genetic changes in the gyrA, rpoB and katG genes were more consistently associated with a significant resistance phenotype. Despite this, however, a considerable proportion of resistant MTB isolates were found to harbour no detectable mutations in the corresponding gene loci. CONCLUSIONS: These findings expand the spectrum of potential resistance-related mutations in MTB clinical isolates and help consolidate the framework for the development of molecular methods for delineating the drug susceptibility profiles of MTB isolates in clinical laboratories.