# Chemical probes of mycobacterial growth and persistence

> **NIH NIH F32** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2021 · $68,562

## Abstract

PROJECT SUMMARY/ABSTRACT
The bacillus Mycobacterium tuberculosis (Mtb) is the etiological agent of tuberculosis (TB) in humans. Despite
a steady decline in TB mortality rates, multidrug resistant TB (MDR-TB) and relapse cases have increased. These
observations highlight the urgent yet unmet need to understand how MDR-TB develops and persists. Moreover,
new strategies to diagnose and treat Mtb infection can limit the spread of the disease and therefore the spread of
resistance. Despite these needs, the mechanisms by which Mtb evades treatment remain insufficiently defined, in
part due to a lack of tools available to probe Mtb physiology. Strategies that could mitigate these problems include
early diagnosis, an understanding of variation in division rate between cells, and insight into Mtb persistence.
Distinguishing phenotypic heterogeneity is difficult using traditional transcriptomics; chemical biology can yield
tools to detect mycobacteria and monitor the dynamics of cell division. We have developed a fluorogenic probe
(QTF) that reports on mycobacterial cell envelope assembly in real time. I shall employ QTF to identify and
characterize distinct spatial and temporal profiles of bacteria from the Corynebacterineae suborder. Because QTF
is activated by mycolyltransferase activity, fluorescence kinetics will be used for diagnostic purposes to identify
and separate mycobacteria and corynebacteria in mixed microbial communities. I will also evaluate QTF in an
isogenic monoculture, as I postulate this probe can be used to separate normal from persister cells. Finally, I shall
develop a new fluorogenic probe, complementary to QTF, that will covalently label the growing cell wall. I
envision QTF and this probe can simultaneously monitor mycolyltransferase activity cell envelope construction
and remodeling.

## Key facts

- **NIH application ID:** 10136640
- **Project number:** 5F32GM133116-03
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Michael G Wuo
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $68,562
- **Award type:** 5
- **Project period:** 2019-05-20 → 2022-05-19

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10136640

## Citation

> US National Institutes of Health, RePORTER application 10136640, Chemical probes of mycobacterial growth and persistence (5F32GM133116-03). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10136640. Licensed CC0.

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