Genetic variability, genotyping, and genomics of Mycobacterium leprae

Leprosy, caused by Mycobacterium leprae and Mycobacterium lepromatosis, remains a significant global health issue despite a tremendous decline in its worldwide prevalence in the last four decades. Mycobacterium leprae strains possess very limited genetic variability, making it difficult to distinguish them using traditional genotyping tools. Successful genome sequencing of a considerable number of M. leprae strains in the recent past has allowed development of improved genotyping tools for the molecular epidemiology of leprosy. Comparative genomics has identified distinct M. leprae genotypes and revealed their characteristic genomic markers. This review summarizes the progress made in M. leprae genomics, with special emphasis on the development of genotyping schemes. Further, an updated genotyping scheme is introduced that also includes the newly reported genotypes 1B_Bangladesh, 1D_Malagasy, 3K-0/3K-1, 3Q and 4N/O. Additionally, genotype-specific markers (single nucleotide polymorphisms, Insertion/Deletion) have been incorporated into the typing scheme for the first time to enable differentiation of closely related strains. This will be particularly useful for geographic regions where M. leprae strains characterized by a small number of genotypes are predominant. The detailed compilation of genomic markers will also enable accurate identification of M. leprae genotypes, using targeted analysis of variable regions. Such markers are good candidates for developing artificial intelligence-based algorithms for classifying M. leprae genomic datasets.