Completed Infection & Immunity Cells, Biochemistry & Physiology

Understanding the role of sugar transporters in Mycobacterium tuberculosis.

Funder Wellcome Charity-funded
Recipient organisation University of Manchester
Funding £1.8M
Period Jul 2016 — Jan 2026

In plain English

AI plain-English summary

Tuberculosis bacteria are stealing sugar from their human hosts, and researchers want to catch them in the act. The bacterium *Mycobacterium tuberculosis* (Mtb) needs sugar to build its protective cell wall and fuel its growth inside the body. Scientists know that Mtb has proteins on its surface that import sugar, but they do not know exactly which sugars each transporter grabs, how the proteins are built, or whether shutting them down would stop an infection. This project will produce those transporter proteins in the lab, determine their crystal structures, and identify the specific sugars they bind. The team will also create mutant bacteria that lack individual sugar transporters and track whether those mutants can still infect mice. This is fundamental science. It asks how a major pathogen feeds itself, with no immediate clinical application. But understanding the molecular gateways Mtb uses to get its fuel could eventually point to new drug targets. If a compound can block a sugar transporter, it might starve the bacterium without harming human cells, which use different sugar import systems. Similar work on bacterial nutrient uptake has previously revealed vulnerabilities exploited by existing antibiotics.

View original technical description
There is currently a lack of understanding of the role of the sugar transport systems in Mycobacterium tuberculosis. The aim of the project is to elucidate the role of these sugar transporters in Mtb by undertaking an interdisciplinary state-of-the-art biochemical, chemical and genetic approach. In this project proteins involved in the uptake of sugars will be recombinantly expressed with the goal of biochemically characterizing the specific substrates that bind and determining the crystal struc ture of these proteins in complex with their physiological ligands, with a view to developing inhibitors of these systems. In parallel a series of mutants of genes involved in sugar uptake will be generated in order to assess the functional role of the transporters and the effects of these mutations determined in vitro by tracking the accumulation of sugars and their incorporation into the cell wall of mycobacteria and in vivo in mice to understand their role in virulence and infection. The mai n goals are: 1) Biochemical characterization and structural determination of the enzymes involved in sugar uptake. 2) Assign physiological functions to genes involve in sugar transport by generating null and conditional mutants in mycobacteria.

View the original record at the funder ↗

Researchers

Elizabeth Fullam (EPMC Awardee)

Related Research

Grants with similar aims, by meaning.

Understanding the role of sugar transporters in Mycobacterium tuberculosis
Molecular Basis of Sugar Transport in Mycobacterium tuberculosis
Uncovering the mechanisms of ABC transporter glycoconjugate translocation in Mycobacterium tuberculosis and their roles in virulence.
Mapping nutrient uptake and processing in Mycobacterium tuberculosis
Uncovering Nutrient Acquisition and Metabolism in Mycobacterium tuberculosis.

Original classification

Sir Henry Dale Fellowship

Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.