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Updated: Jul 15, 2026

Assay Development for High-Throughput Drug Screening Against Mycobacteria
Published on: October 25, 2024
Cefpiramide Restricts Mycobacterium tuberculosis Growth by Binding to the DNA-Binding Domain of an Essential Response
Siranjeevi Rangaraj1, Shalini Saxena1,2, Vidya Chitta Voina1
1Department of Biochemistry, School of Life Sciences, University of Hyderabad, Hyderabad, Telangana 500046, India.
Abstract:
The rise in drug-resistant Mycobacterium tuberculosis (M.tb) necessitates new therapeutic strategies. Hypothesizing that a single compound targeting multiple M.tb proteins would make resistance less likely to evolve, we focused on identifying a single compound targeting multiple M.tb OmpR family two-component response regulators (RRs). We screened ∼8000 FDA-approved DrugBank compounds using computational tools (active-site prediction, receptor-ligand docking, and molecular dynamics simulations) to identify one compound acting on M.tb RRs: MtrA, PrrA, MprA, RegX3, and PhoP. Cefpiramide showed strong docking scores and favorable interactions with all five RRs. Experimental validations confirmed that cefpiramide binds MtrA and RegX3 with K b values of 109.69 ± 27.99 nM-1 and 113.49 ± 36.63 nM-1, respectively. Further, the disruption of transcription repressor function of MtrA is possibly by disruption of its DNA binding property, as mutant analysis indicated that cefpiramide targets the DNA-binding domain of MtrA. Cefpiramide inhibited M.tb H37Rv growth (MIC50 = 4 ± 2.38 μg/mL), warranting further investigation as a component of combinatorial tuberculosis therapy.
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