PurFect timing: revisiting purine metabolism for tuberculosis treatment

Richard J Wall; Valerie Mizrahi; Dirk A Lamprecht

doi:10.1016/j.tim.2025.10.010

PurFect timing: revisiting purine metabolism for tuberculosis treatment

Trends Microbiol. 2026 Jan;34(1):31-33. doi: 10.1016/j.tim.2025.10.010. Epub 2025 Nov 6.

Authors

Richard J Wall¹, Valerie Mizrahi², Dirk A Lamprecht³

Affiliations

¹ Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, WC1E 7HT, UK. Electronic address: richard.wall@lshtm.ac.uk.
² Molecular Mycobacteriology Research Unit, Institute of Infectious Disease and Molecular Medicine & Department of Pathology, University of Cape Town, Cape Town, South Africa.
³ Holistic Drug Discovery and Development (H3D) Centre, University of Cape Town, Rondebosch, 7700, Cape Town, South Africa.

PMID: 41203488
DOI: 10.1016/j.tim.2025.10.010

Abstract

Eradication of tuberculosis requires new drugs targeting novel pathways. Although purine metabolism represents an essential antitubercular target, concerns about host nucleobase rescue limited its exploration. New data demonstrate that nucleobase levels in human lung tissue are insufficient to confer rescue, renewing interest in this pathway for tuberculosis drug discovery.

Keywords: drug discovery; metabolism; nucleobase; purine salvage; tuberculosis.

MeSH terms

Antitubercular Agents* / pharmacology
Antitubercular Agents* / therapeutic use
Drug Discovery
Humans
Lung / metabolism
Lung / microbiology
Mycobacterium tuberculosis* / drug effects
Mycobacterium tuberculosis* / metabolism
Purines* / metabolism
Tuberculosis* / drug therapy
Tuberculosis* / metabolism
Tuberculosis* / microbiology

Substances

Purines
Antitubercular Agents
purine