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bioRxiv · 10.1101/2025.11.20.689507

Rv3400 is a phosphoglucomutase required for trehalose metabolism in Mycobacterium tuberculosis

Liu, Y.·Ruecker, N.·Faulkner, V.·Rachineni, K.·Al-Saffar, N.·VillacampaTeixeira, P.·Dias da Costa, T.·Johnson, E.·Robertson, B. D.·Ehrt, S.·Larrouy-Maumus, G.
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Abstract

Mycobacterium tuberculosis is a global killer causing over a million deaths from tuberculosis (TB) every year. It is therefore a major burden on human health. To reduce the deadly impact of TB, we need a better understanding of the strategies used by M. tuberculosis to adapt its metabolism to survive and persist in the human host. This will help us design better strategies for TB treatment and control. Previous enzymological studies have reported the Mtb rv3400 gene as encoding a {beta}-phosphoglucomutase; however, its role in M. tuberculosis metabolism was not investigated. In the present study, we show that deletion of rv3400 leads to a 30-fold increase in {beta}-D-glucose 1-phosphate, confirming its primary function as a {beta}-phosphoglucomutase. Additionally, deletion of rv3400 leads to a growth defect when trehalose is the sole carbon source indicting that this enzyme is required for optimal use of trehalose, an essential disaccharide in mycobacteria. ImportanceTrehalose metabolism plays a corner stone in Mycobacterium tuberculosis physiology and virulence. Hence, a better understanding of the metabolism of this essential disaccharide is required to develop novel strategies to eradicate Tuberculosis. Here we report on the characterisation of the strain lacking a {beta}-phosphoglucomutase, encoded by the gene rv3400. We show that deletion of rv3400 leads to an increase of {beta}-D-glucose 1-phosphate and a growth defect when using trehalose as sole carbon source. Taken together, the data presented here provide evidence that Rv3400 is required for the catabolism of trehalose.

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Liu, Y., Ruecker, N., Faulkner, V., Rachineni, K., Al-Saffar, N., VillacampaTeixeira, P., Dias da Costa, T., Johnson, E., Robertson, B. D., Ehrt, S., Larrouy-Maumus, G.. 2025-11-20. Rv3400 is a phosphoglucomutase required for trehalose metabolism in Mycobacterium tuberculosis. https://doi.org/10.1101/2025.11.20.689507

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