# Tailoring modifications of polysaccharides in Mycobacterium tuberculosis

> **NIH NIH R01** · COLORADO STATE UNIVERSITY · 2023 · $637,594

## Abstract

Abstract
The covalent modification of prokaryotic cell envelope glycans, namely lipopolysaccharide (LPS) and
(lipo)teichoic acids, with discrete substituents such as sugars, amino acids, phosphates or acyl groups, is a
well-known strategy used by Gram-negative and Gram-positive bacteria to modulate their cell surface
properties, the way they interact with their environment, their resistance to biocides and host defenses, and
pathogenicity. Although evidence exists that Mycobacterium tuberculosis (Mtb) similarly decorates its major
cell envelope glycans, arabinogalactan (AG) and lipoarabinomannan (LAM), with various tailoring substituents,
little is known of their biological significance. The discovery by our laboratories of the biosynthetic machineries
responsible for the synthesis and transfer of these discrete motifs to AG and LAM, and the generation of the
first Mtb knock-out mutants deficient in their biosynthesis have opened the way to studies aimed at
understanding the function of these motifs in the physiology and immunopathogenesis of Mtb. We
hypothesize that Mtb has evolved to modify its cell-envelope glycans with a distinct array of
strategically placed substituents to promote its survival in the host environment. Accordingly, a
multidisciplinary team of investigators with complementary expertise in mycobacterial cell envelope genetics
and glycobiology, TB immunopathogenesis, and carbohydrate chemistry here proposes to investigate how
simple (amino/thio)sugars or other charged groups strategically placed within the Mtb cell envelope landscape
affect not only the physiology of this microorganism (Aim 1), but also the course of pulmonary infection,
pathology and development of innate and adaptive immunity in infected C3HeB/FeJ mice (Aim 2), and the
interactions of Mtb with host macrophages and dendritic cells thereby promoting survival within the host (Aim
3). Ultimately, these studies are expected to lead to significant new knowledge about the biological significance
of understudied aspects of the unique cell wall of mycobacteria.

## Key facts

- **NIH application ID:** 10685409
- **Project number:** 5R01AI167204-03
- **Recipient organization:** COLORADO STATE UNIVERSITY
- **Principal Investigator:** Mercedes Gonzalez-Juarrero
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $637,594
- **Award type:** 5
- **Project period:** 2021-09-17 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10685409

## Citation

> US National Institutes of Health, RePORTER application 10685409, Tailoring modifications of polysaccharides in Mycobacterium tuberculosis (5R01AI167204-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10685409. Licensed CC0.

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