# Novel aminoglycoside adjuvants and stand-alone agents to combat tuberculosis

> **NIH NIH R01** · UNIVERSITY OF KENTUCKY · 2021 · $548,046

## Abstract

ABSTRACT
Tuberculosis (TB) is the deadliest global infection (1.4 million deaths in 2015), having recently surpassed
HIV/AIDS. ~250,000 of these deaths were from multidrug-resistant (MDR) TB, with only ~50% success in
treatment of MDR-TB. Unless new strategies to combat or prevent emergence of drug-resistant TB are
found, the global spread of MDR-TB will be an epidemic of epic proportions. Kanamycin A (KAN) is an
antibiotic of last resort used to treat MDR-TB. Resistance to KAN signifies extensively drug-resistant
(XDR) TB, which is nearly incurable. One-third of KAN-resistant TB is caused by upregulation of the
acetyltransferase Eis in Mycobacterium tuberculosis (Mtb), caused by mutations in the eis promoter. We
investigated the mechanism of Eis and discovered and validated several Eis inhibitor scaffolds in the
previous funding period. In Aims 1 and 2 of this application, we propose to develop a novel strategy to
combat and forestall KAN resistance in TB. These Aims are focused on the preclinical development of
these Eis inhibitors for their ultimate use as a combination therapy with KAN against MDR-TB. In Aim 3,
we propose to determine the mechanism(s) of the anti-Mtb activity of novel compounds that were
discovered to inhibit Eis and potently inhibit Mtb bacteria without KAN, ultimately to develop them as
therapeutics against both drug-resistant and drug-resistant TB.

## Key facts

- **NIH application ID:** 10188396
- **Project number:** 5R01AI090048-10
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** Sylvie Garneau-Tsodikova
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $548,046
- **Award type:** 5
- **Project period:** 2011-08-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10188396

## Citation

> US National Institutes of Health, RePORTER application 10188396, Novel aminoglycoside adjuvants and stand-alone agents to combat tuberculosis (5R01AI090048-10). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10188396. Licensed CC0.

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