DapB is a conserved target for tackling antimicrobial resistance in Mycobacterium tuberculosis.

Tuberculosis (TB) remains a major global health issue, with growing challenges posed by drug resistance, highlighting the urgent need to identify new drug targets. This study examines the conservation pattern of the dapB gene, which encodes Dihydrodipicolinate reductase (DapB), a key enzyme in the lysine biosynthesis pathway of Mycobacterium tuberculosis (Mtb), a pathway absent in humans. The dapB gene was amplified from 72 Indian clinical isolates, sequenced and analysed for mutations. Further, the genomic data of 310 isolates from the Bacterial and Viral Bioinformatics Resource Center (BV-BRC) database were also analysed. Further, atomistic simulations were performed in triplicate for the wild-type and mutant proteins to assess the impact of mutations on protein structure and function. Sequence analysis identified a single DapB mutation (DapB_65), among clinical isolates. Analysis of BV-BRC isolates revealed two synonymous mutations and one non-synonymous mutation (DapB_89). The mutations were mapped on the surface of the protein and were found to be more than 1.0 nm away from the active site. Simulations reveal no significant difference in the overall structure or the binding pocket dimensions and volumes between the native and mutant proteins. This study thus highlights the potential of DapB as a conserved drug target for future drug development efforts aimed at TB.