The significance of persisters in tuberculosis drug discovery: Exploring the potential of targeting the glyoxylate shunt pathway.

Eur J Med Chem

Infectious Diseases Division, CSIR- Indian Institute of Integrative Medicine, Jammu, 180001, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India. Electronic address:

Published: February 2024

The significant challenge in confronting TB eradication is the discursive treatment that results in the disease reactivation, patient non compliance and drug resistance. The presently available drug regimen for TB largely targets the active bacilli and thus remains inadequate against the dormant or persistent subpopulation of Mtb that results in latent TB affecting a quarter of the global population. The crucial pathways that are particularly essential for the survival of dormant Mtb demand better apprehension. Novel drugs are needed to specifically address these persisters in order to enhance treatment effectiveness. Among such pathways, the glyoxylate bypass plays a critical role in the persistence and latent infection of Mtb, making it a promising target for drug development in recent years. In this review, we have compiled the attributes of bacterial subpopulations liable for latent TB and the pathways indispensable for their survival. Specifically, we delve into the glyoxylate shunt pathway and its key enzymes as potential drug targets.

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http://dx.doi.org/10.1016/j.ejmech.2023.116058DOI Listing

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Article Synopsis
  • - The study investigates biofilm formation in a bacterial strain from coastal seawater, finding that biofilm cells have higher antibiotic resistance compared to their free-floating counterparts.
  • - Through transcriptome analysis, researchers identified 685 upregulated and 517 downregulated genes in biofilm cells, linking the upregulated genes to pathways like glyoxylate metabolism, while downregulated genes were associated with flagellar assembly.
  • - The key gene AceA, involved in the glyoxylate shunt, plays a crucial role in biofilm maintenance and dispersal, revealing insights into the genetic mechanisms of biofilm formation and its implications for environmental issues and public health.
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