The metallophosphoesterase Rv0805 regulates carbon flux and cell envelope homeostasis during growth of mycobacteria in propionate
Author(s)
Type
Journal Article
Abstract
Mycobacterium tuberculosis relies on host-derived lipids, including cholesterol, for intracellular survival, generating propionyl-CoA—a metabolite that must be efficiently assimilated to prevent toxicity. The metallophosphoesterase Rv0805 is required for optimal growth on cholesterol, and an Rv0805 knockout strain exhibits impaired ability to colonize the murine lung. However, the mechanisms underlying the essential role of Rv0805 under host-relevant conditions remain unclear. The deletion of the rv0805 ortholog (bcg_0857) in Mycobacterium bovis BCG reveals that both its catalytic activity and membrane localization are essential for growth on propionate, a by-product of cholesterol metabolism. Loss of Rv0805 impaired propionate uptake, altered cell envelope lipid composition with an accumulation of methyl-branched lipids, and reduced carbon flux through the methylcitrate cycle, ultimately depleting key central carbon metabolites required for growth. Vitamin B12 supplementation activated the methylmalonyl pathway, restoring metabolic balance and rescuing growth. These findings demonstrate that Rv0805 links propionate metabolism with cell envelope integrity, identifying its activity and localization as metabolic vulnerabilities that could be exploited for tuberculosis therapy.
Editor(s)
Champion, Patricia A
Date Issued
2026-03-19
Date Acceptance
2026-02-02
Citation
Journal of Bacteriology, 2026, 208 (3)
ISSN
0021-9193
Publisher
American Society for Microbiology
Journal / Book Title
Journal of Bacteriology
Volume
208
Issue
3
Copyright Statement
© 2026 Biswas et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/41757903
Subjects
Mycobacterium tuberculosis
Rv0805 metallophosphoesterase
cell wall integrity
methylcitrate cycle
propionate metabolism
Homeostasis
Carbon
Propionates
Mycobacterium bovis
Bacterial Proteins
Cell Wall
Mycobacterium tuberculosis
Gene Expression Regulation, Bacterial
Cell Membrane
Mice
Animals
Publication Status
Published
Coverage Spatial
United States
Article Number
e00571-25
Date Publish Online
2026-02-27