Molecular Characterization of Mycobacterial Ribonucleotide Reductase (RNR) and its Implication as a Novel Drug Target

Abstract

The genus Mycobacterium consists of both pathogenic and non-pathogenic species. The emergence of MDR and XDR tuberculosis and opportunistic infections by non tuberculous mycobacterium in immunosuppressive persons are major concern now a days. The aim of the study was to characterize ribonucleotide reductase (RNR) of Mycobacterium species to produce information about the evolution of the gene which could further be used in targeting RNR as a novel drug target. Here we were analyzed RNR of 23 mycobacterial species. The sequence length of RNR region is about 975 bp. Out of 975 characters 625 (64.10%) are conserved sites (monomorphic) and 350 (35.89%) are variable sites (polymorphic). The total nucleotide diversity (π) is=0.120114 (12.011%). The RNR phylogeny approach in Mycobacterium species provides evidence of several evolutionary lineages evolving from the ancestral polymorphism and fixed in the descendant population. Species of mycobacteria causing tuberculosis or respiratory infection in humans have specific patterns of allele distribution in different motifs, which differentiate them from other opportunistic mycobacterial species. Molecular analysis and structural motif analysis of RNR suggests the occurrence of host-mediated genetic differentiation in mycobacterial species, which requires further wet lab investigations.