# Mycobacterial trehalose metabolism as drug targets

> **NIH NIH R01** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2020 · $432,647

## Abstract

Goal: The overarching goal of this proposal is to better understand key steps in the utilization and
recycling of trehalose in mycobacteria.
The disaccharide trehalose is important for multiple aspects of mycobacterial physiology and has been
shown to be essential for viability as is the downstream utilization pathway that leads to trehalose
monomycolate production and export. Recycling of the trehalose used to build the outer membrane is
important for M. tuberculosis virulence and is used to extend a-glucans that have various roles in the
bacterium. This research project possesses 2 separate portions related to trehalose metabolism. The first
portion of this study aims to develop novel classes of compounds that inhibit the three enzymes of the
Antigen 85 Complex. Second, we will use our current knowledge of GlgE protein structure to develop
second-generation inhibitors and improved tools for assessing the inhibitor activity of these inhibitors. Since
inhibition of GlgE promotes rapid killing of M. tuberculosis, improving upon the current inhibitors will
significantly advance our ability to treat TB. It is expected that results obtained from this study will extend
the available M. tuberculosis drugs to include compounds that target trehalose biosynthesis and utilization.

## Key facts

- **NIH application ID:** 9969309
- **Project number:** 5R01AI105084-08
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** Donald R Ronning
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $432,647
- **Award type:** 5
- **Project period:** 2018-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9969309

## Citation

> US National Institutes of Health, RePORTER application 9969309, Mycobacterial trehalose metabolism as drug targets (5R01AI105084-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9969309. Licensed CC0.

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