# Chemical Probes of Mycobacteria

> **NIH NIH R01** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2024 · $579,261

## Abstract

Project Summary/Abstract Section
The rise of resistant strains of Mycobacterium tuberculosis (Mtb) demands new approaches to
combating this infectious agent. The survival of Mtb depends on the cell envelope, which is both
durable and dynamic. Mycobacteria modulate their cell envelope composition to subsist in the
harsh environments they encounter in the host. The proposed aims focus on developing new
tools to probe, perturb, and observe changes in the mycobacterial cell envelope. The focus of
Aim 1 is on visualizing arabinofuranose and mannose residues within the cell wall and the
immunomodulatory lipoarabinomannan (LAM). In Aim 2, we shall develop a complementary
probe that identifies methylthioxylofuranose (MTX)-capped LAM, a glycan that has been
detected in pathogenic mycobacteria. The probes generated in Aims 1 and 2 can reveal how cell
envelope composition varies under different conditions and between strains. In Aim 3, we shall
deploy a fluorogenic probe to visualize the changing mycobacterial cell envelope in real time.
This probe provides a means to explore phenotypic changes in the mycobacterial cell envelope
upon antibiotic treatment or uptake into macrophages. By pursuing the three aims, we expect to
uncover vulnerabilities in mycobacterial defenses that will lead to new antibiotic strategies.
Significance:
The overall objective of this application is to develop new chemical probes to understand how
the mycobacteria modify and maintain their cell envelope to survive under the extreme and
varied conditions they encounter in human hosts. We anticipate that this knowledge will
ultimately lead to the identification of new strategies to treat tuberculosis (TB).

## Key facts

- **NIH application ID:** 10811587
- **Project number:** 5R01AI126592-09
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Laura L Kiessling
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $579,261
- **Award type:** 5
- **Project period:** 2017-02-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10811587

## Citation

> US National Institutes of Health, RePORTER application 10811587, Chemical Probes of Mycobacteria (5R01AI126592-09). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10811587. Licensed CC0.

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