ArticleMetabolomics : Official journal of the Metabolomic Society2025
Mycobacterium tuberculosis curli pili facilitates pathogenicity by modulating central carbon metabolism.
Article in Metabolomics : Official journal of the Metabolomic Society, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Combination strategies targeting multiple ETC subunits as a rational approach for drug-resistant TB therapy.Archives of microbiology · 2026Review
- Mycobacterium tuberculosis bacteriology and immunity necessitate a multi-pronged immune strategy for vaccination.NPJ vaccines · 2026Review
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Authors and funding
6 authors.
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Abstract
introductionStrategies specifically targeting the initial host-pathogen interactions, hold great promise in the identification of accurate biomarkers for tuberculosis (TB) prevention interventions. Mycobacterium tuberculosis (Mtb) curli pili (MTP) (encoded by mtp/Rv3312A), a surface adhesin utilised by the pathogen to interact with host receptor cells, has been reported as a suitable target for TB diagnostic and therapeutic strategies. Previous "omics" studies highlighted the role MTP potentially plays in Mtb central carbon metabolism (CCM). However, its precise contribution to metabolism remains unknown.
objectivesThis study aimed to examine the role of MTP in the bioenergetic metabolism of Mtb, using bedaquiline (BDQ) to inhibit ATP production through oxidative phosphorylation (OXPHOS), extracellular flux analysis, Mtb wildtype (WT), ∆mtp deletion mutant, and mtp-complemented strains. The role of MTP in regulation of CCM was assessed using
resultsMTP was associated with increased bacterial respiration and decreased carbon catabolism via glycolysis in response to the inhibition of ATP synthase by BDQ. The dependence of Mtb Δmtp on OXPHOS for energy production was demonstrated to be greater than the WT and mtp-complemented strains. In addition, metabolic flux profiles revealed that in the Δmtp mutant, CCM was dysregulated by decreasing flux through glycolysis, tricarboxylic acid cycle, glyoxylate and dicarboxylate metabolism, and the pentose phosphate pathway in comparison to the WT.
conclusionThese novel findings show that MTP is associated with the regulation of bioenergetics and metabolism pathways and substantiate MTP as a potential biomarker for TB diagnostics/therapeutics, and a novel target for vaccine/drug development.
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