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 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 tuberculosis. Supplementary Material File (manuscript.docx) - Download - 1.75 MB Information & Authors Information Version history Peer review timeline Published Journal of Biomolecular Structure and Dynamics Version of Record6 Nov 2025Published Copyright This work is licensed under a Non Exclusive No Reuse License.

Authors Metrics & Citations Metrics Article Usage 304views 95downloads Citations Download citation Pratik Mahajan, Hetarth Gor, Manali Joshi, et al. DapB is a conserved target for tackling antimicrobial resistance in Mycobacterium tuberculosis. Authorea. 10 July 2025. DOI: https://doi.org/10.22541/au.175217236.64777388/v1 DOI: https://doi.org/10.22541/au.175217236.64777388/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu.