# Mycobacterium tuberculosis methylglucose lipopolysaccharides

> **NIH NIH R21** · COLORADO STATE UNIVERSITY · 2020 · $228,000

## Abstract

Project Summary
Mycobacteria produce two unusual polymethylated polysaccharides (PMPS), the 3-O-methylmannose
polysaccharides (MMP) and the 6-O-methylglucose lipopolysaccharides (MGLP). Both polysaccharides are
located in the cytoplasm where they have been postulated to regulate fatty acid and mycolic acid metabolism
as a consequence of their ability to form stable 1:1 complexes with long-chain fatty acids and acyl-coenzyme A
derivatives. These findings, however, have been derived from in vitro studies using purified polysaccharides
and fatty acids and it is at present unclear whether they accurately reflect the physiological relevance of PMPS
in intact mycobacterial cells.
Studies initiated by our laboratory have begun to shed light on the nature of the enzymes involved in MGLP
biosynthesis and to yield the first recombinant strains defective in various aspects of MGLP biosynthesis.
Preliminary analyses of these strains point to an important role of MGLP in the adaptation of Mycobacterium
tuberculosis and Mycobacterium smegmatis to thermal stress. Consistent with this observation, earlier work by
Dr. Ballou and associates revealed that a M. smegmatis strain partially deficient in PMPS production displayed
altered levels of unsaturated fatty acids. Taken together, these results are suggestive of the existence of a
rather unique mechanism used by mycobacteria to control fatty acid metabolism in response to stress.
Whether MGLP are essential for mycobacterial growth is currently unknown as none of the mutants generated
so far were totally defective in MGLP biosynthesis and their growth was only tested under a limited number of
laboratory conditions. Likewise, the precise function of MGLP in the fatty metabolism of intact cells remains
essentially undefined since mutant characterization thus far has been restricted to the analysis of steady-state
levels of fatty acids under conditions where MGLP may not be required for optimal growth, and has neither
thoroughly analyzed longer acyl chains such as mycolic acids, addressed de novo synthesis of fatty acids and
mycolic acids, or analyzed lipid contents.
We propose under Aim 1 to knock-out or knock-down in M. tuberculosis a number of MGLP biosynthetic genes
that we identified so as to determine whether MGLP are required for growth under a variety of conditions
thought to mimic the physical environments encountered by M. tuberculosis during host infection. Under Aim
2, we will use these mutants as well as other recombinant strains presenting various quantitative or qualitative
defects in MGLP synthesis that we will generate to shed light on the physiological function(s) of these
polysaccharides with a particular focus on fatty acid, mycolic acid and lipid metabolism. In addition to
advancing our understanding of a novel and potentially critical physiological process of mycobacteria, our
proposed studies may prove useful in designing innovative and Mycobacterium-specific therapeutic strategies
for the trea...

## Key facts

- **NIH application ID:** 9848499
- **Project number:** 5R21AI144344-02
- **Recipient organization:** COLORADO STATE UNIVERSITY
- **Principal Investigator:** Mary Jackson
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $228,000
- **Award type:** 5
- **Project period:** 2019-01-09 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9848499

## Citation

> US National Institutes of Health, RePORTER application 9848499, Mycobacterium tuberculosis methylglucose lipopolysaccharides (5R21AI144344-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9848499. Licensed CC0.

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