Genotypic investigation of Mycobacterium leprae in patients with relapsing leprosy in Mato Grosso, Brazil
摘要
Leprosy is a chronic disease that leads to significant neurological damage and disabilities. Drug resistance is a major challenge in controlling the disease. Mutations in the folP1, rpoB, and gyrA genes can confer resistance to dapsone, rifampicin, and quinolones, respectively. The aim of this study was to identify mutations in these drug-resistance genes in Mycobacterium leprae among patients in the state of Mato Grosso, Brazil, and to investigate potential related clinical characteristics. A total of 60 patients from various cities in Mato Grosso were clinically evaluated. Following skin biopsies, samples underwent bacilloscopy and PCR analysis, resulting in 34 positive samples. Fourteen patients were undergoing multidrug therapy (MDT), and 4 exhibited active reactional states during the investigation. Relapse was identified in 8 patients. High-quality sequences were generated for the rpoB, folP1, and gyrA gene fragments. We observed a single alteration in the gyrA gene sequence, specifically a cytosine-to-thymine transition at position 297. This alteration was detected in 10 patients, all classified as multibacillary. The analysis indicated that 5 of these patients with relapse had bacilli with the gyrA gene polymorphism, including one patient experiencing erythema nodosum leprosum. Another 4 patients were already on their second MDT treatment regimen, and one had been under treatment for 6 months. In conclusion, while classical resistance mutations were not prevalent in the cohort, the identification of synonymous SNPs in the gyrA gene has significant potential as a surrogate marker for particular mycobacterial subpopulations linked to relapse.