ABSTRACT
BACKGROUND: Multidrug resistance is a critical factor in tuberculosis control. To gain better understanding of multidrug resistant tuberculosis in Brazil, a retrospective study was performed to compare genotypic diversity and drug resistance associated mutations in Mycobacterium tuberculosis isolates from a national reference center. METHODS AND FINDINGS: Ninety-nine multidrug resistant isolates from 12 Brazilian states were studied. Drug-resistance patterns were determined and the rpoB and katG genes were screened for mutations. Genotypic diversity was investigated by IS6110-RFLP and Luminex 47 spoligotyping. Mutations in rpoB and katG were seen in 91% and 93% of the isolates, respectively. Codon 315 katG mutations occurred in 82.8% of the isolates with a predominance of the Ser315Thr substitution. Twenty-five isolates were clustered in 11 groups with identical IS6110-RFLP patterns while 74 showed unique patterns with no association between mutation frequencies or susceptibility profiles. The most prevalent spoligotyping lineages were LAM (47%), T (17%) and Haarlen (12%). The Haarlen lineage showed a higher frequency of codon 516 rpoB mutations while codon 531 mutations prevailed in the other isolates. CONCLUSIONS: Our data suggest that there were no major multidrug resistant M. tuberculosis strains transmitted among patients referred to the reference center, indicating an independent acquisition of resistance. In addition, drug resistance associated mutation profiles were well established among the main spoligotyping lineages found in these Brazilian multidrug resistant isolates, providing useful data for patient management and treatment.
Subject(s)
Bacterial Proteins/genetics , Catalase/genetics , Drug Resistance, Multiple, Bacterial/genetics , Mutation/genetics , Mycobacterium tuberculosis/genetics , Mycobacterium tuberculosis/isolation & purification , Tuberculosis, Multidrug-Resistant/genetics , Adult , Bacterial Typing Techniques , Brazil/epidemiology , Cluster Analysis , DNA-Directed RNA Polymerases , Demography , Female , Humans , Incidence , Male , Mycobacterium tuberculosis/classification , Phylogeny , Polymorphism, Restriction Fragment Length , Retrospective Studies , Tuberculosis, Multidrug-Resistant/epidemiologyABSTRACT
A tuberculose continua a figurar como uma das principais enfermidades que afetam a humanidade. A Organizaçäo Mundial de Saúde OMS) estima que cerca de 1/3 da populaçäo mundial esteja infectada pelo Mycobacterium tuberculosis. A pandemia causada pelo HIV contribui muito para o agravamento da situaçäo epidemiológica da tuberculose em todo o mundo. Além disso, o controle da tuberculose também está ameaçado pela emergência de cepas multirresistentes às drogas antituberculostáticas. Assim, estudos epidemiológicos que permitam a diferenciaçäo de cepas de M. tuberculosis säo importantes para o controle da doença por meio da detecçäo de casos índices. Neste trabalho, descrevemos as técnicas de biologia molecular mais utilizadas para a epidemiologia molecular da tuberculose, assim como fazemos uma breve revisäo da literatura com os resultados obtidos na aplicaçäo destas técnicas.
