Mycobacterium leprae 18-kDa heat shock protein gene is polymorphic

Leprosy is still a major health problem in India. Mycobacterium leprae, the organism causing the disease, appears to be genetically invariant. Attempts to identify strain variation in different isolates of M. leprae have met with little success. The M. leprae 18-kDa heat shock protein is a major T-cell antigen, and this protein belongs to the family of small heat shock proteins. In the present study, we have analysed the mRNA expression profiles of 18-kDa gene in lesions across the leprosy spectra by RT-PCR and also sequenced the PCR amplicons prepared from 25 independent leprosy cases. A single nucleotide polymorphism was detected at 154th bp position in this secreted antigen gene. In this gene, codon 52 exists as TCA in about 60% of the samples and as CCA in rest of the leprosy cases. Armadillo-derived M. leprae 18-kDa HSP gene has TCA at the 52nd position. Among the cases examined, we could not detect mixed population of bacteria carrying both classes of genes, indicating the clonal purity of the bacterium in an infected patient. This polymorphism therefore, could be used as a molecular marker in strain typing of M. leprae in endemic populations. In addition, transmission patterns and relapse and/or reinfection in reactional patients could be examined using this polymorphism. Expression of the 18-kDa HSP gene in reactional cases indicates that live bacterium might be contributing to the reactional conditions in leprosy.