Rv3400 is a phosphoglucomutase required for trehalose metabolism in Mycobacterium tuberculosis
File(s)
Accepted version
Author(s)
Larrouy-Maumus, Gerald
Type
Journal Article
Abstract
Mycobacterium tuberculosis causes over one million deaths from tuberculosis (TB) every year and remains a major burden on human health. Reducing the deadly impact of TB requires a better understanding of the strategies used by M. tuberculosis to adapt its metabolism, survive and persist in the human host. Previous enzymological studies reported that the Mtb rv3400 gene encodes a β-phosphoglucomutase; however, its role in M. tuberculosis metabolism had not been investigated. Here, we show that deletion of rv3400 causes a 30-fold increase in β-D- glucose-1-phosphate, confirming its primary function as a β-phosphoglucomutase. Deletion of rv3400 also causes a growth defect when trehalose is the sole carbon source. Targeted metabolomics revealed that metabolites associated with redox homeostasis, including ergothioneine, mycothiol and mycothione, are decreased in the Mtb Δrv3400 strain compared with the wild type, indicating altered tolerance to redox stress. Consistent with this, the Δrv3400 strain showed increased susceptibility to oxidative stress induced by H2O2 and cumene hydroperoxide, conditions that Mtb encounters during infection. This work advances our understanding of trehalose metabolism in Mtb and suggests that Rv3400 may represent a target for the development of new antimicrobial therapies.
Date Acceptance
2026-07-29
Citation
Journal of Bacteriology
ISSN
0021-9193
Publisher
American Society for Microbiology
Journal / Book Title
Journal of Bacteriology
Copyright Statement
Copyright This paper is embargoed until publication. Once published the author’s accepted manuscript will be made available under a CC-BY License in accordance with Imperial’s Research Publications Open Access policy (www.imperial.ac.uk/oa-policy).
License URL
Publication Status
Accepted