Exploiting Bacterial DNA Repair Systems as Drug Targets: A Review of the Current Scenario with Focus on Mycobacteria

Taran Khanam, Ravishankar Ramachandran

Abstract


Bacterial DNA repair systems as a drug target have been drawing increasing attention. Recent research has highlighted important differences between bacteria and humans in these systems. Additionally, most existing drugs are not known to act through inhibition of the components of these systems, especially involving the principal replicative ligase, and hence afford the possibility to develop new therapeutics that can overcome present problems of drug resistance. Recent work has highlighted significant differences in DNA repair systems between mycobacteria and others like E. coli, leading to the possibility of developing inhibitors that can distinguish even between these bacteria. In this review, present information on these systems from the point of view of new antibacterial development in general is collated. The subsequent focus is on mycobacterial DNA repair systems, particularly those involving DNA ligases. Presently available inhibitor scaffolds and new approaches for the development of potent inhibitors are also discussed.

Keywords


MtbLigA; NAD+-dependent DNA ligase from M. tuberculosis; BER; Base-excision repair pathway; NER; Nucleotide excision repair pathway; NHEJ; Non-homologous end-joining pathway; HR; Homologous recombination

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