RESUMO
Mexico is a country with sporadic leprosy cases, and the reemergence of drug resistance is a concern. In this study, molecular analysis of Mycobacterium leprae was employed to clarify the spread of drug-resistant leprosy. Thus, drug resistance-determining regions in the folP1, rpoB, and gyrA genes, which are associated with resistance to dapsone, rifampicin, and ofloxacin, respectively, were analyzed by direct sequencing of the PCR product. No mutations in the folP1 gene were observed in any of the 72 slit skin samples obtained from 38 patients, although two samples carrying a mutation at codon 425 in the rpoB gene, which confers resistance to rifampicin, a key component of multidrug therapy, were identified. In addition, a mutation at codon 91 in the gyrA gene, which correlates with ofloxacin resistance, was found in one sample. These results demonstrate the existence of rifampicin- and ofloxacin-resistant leprosy. Interestingly, wild-type and mutant sequences in the gyrA gene were found to coexist in one clinical sample. In addition, all three drug resistance-related mutations were found in only one of the two earlobes of the patients concerned, suggesting a possible pathway for the spread of drug-resistant M. leprae.
Assuntos
Farmacorresistência Bacteriana/genética , Hansenostáticos/farmacologia , Hanseníase/epidemiologia , Hanseníase/microbiologia , Mycobacterium leprae/efeitos dos fármacos , Proteínas de Bactérias/genética , DNA Girase/genética , DNA Bacteriano/análise , DNA Bacteriano/genética , Dapsona/farmacologia , Dapsona/uso terapêutico , Quimioterapia Combinada , Orelha Externa/microbiologia , Humanos , Hansenostáticos/uso terapêutico , Hanseníase/tratamento farmacológico , México/epidemiologia , Mutação , Mycobacterium leprae/genética , Ofloxacino/farmacologia , Ofloxacino/uso terapêutico , Reação em Cadeia da Polimerase , Prevalência , Rifampina/farmacologia , Rifampina/uso terapêutico , Análise de Sequência de DNARESUMO
OBJECTIVE: To classify Mycobacterium leprae isolates from multiple areas in Mexico based on variable number of tandem repeats of 6 base within the rpoT gene and three single nucleotide polymorphism (SNP), and to analyse their geographic distribution in the context of the origin of leprosy in Mexico. RESULTS: Analysis for rpoT genotyping of 64 samples collected in the west and southwestern areas revealed that 46 isolates were of the 4 copy type and 18 isolates were of the 3 copy type. All samples from the eastern coastal area (n = 24) and from the Yucatan peninsula (n = 12) were of the 3 copy type. Six isolates from the west and southwestern area were SNP-type 1, 13 isolates were SNP-type 2 and 45 isolates were SNP-type 3. Nineteen of 24 isolates from the eastern coastal area were SNP-type 3 and one was SNP-type 4. Seven isolates from the Yucatan peninsula were SNP-type 3 and one was SNP-type 4. CONCLUSION: The difference of the proportion of each genotype between the western areas and the eastern areas indicated the expansion of leprosy through different paths in Mexico.