# Adjunct therapeutic potential of a repurposed drug inhibiting Mycobacterium abscessus biofilm formation

> **NIH NIH R21** · COLORADO STATE UNIVERSITY · 2020 · $228,000

## Abstract

Abstract
The prevalence of pulmonary nontuberculous mycobacterial (NTM) infections caused by Mycobacterium
abscessus complex (MABSC) species is increasing worldwide and poses a particular threat to susceptible
individuals with structural or functional lung conditions such as cystic fibrosis (CF), chronic obstructive
pulmonary disease and bronchiectasis. The intrinsic recalcitrance of these pathogens to chemotherapeutic
treatments, and alarming treatment failure rates place a high priority on the development of more effective
treatment approaches.
Although MABSC is known to form microaggregates or biofilms in the thickened alveolar walls, airways and
lung cavity of patients, the precise contribution of biofilm formation to MABSC infection and recalcitrance to
drug treatment has never been clearly established. Using clinically approved drugs thought to target a key
transcriptional regulator (DosRS) required for mycobacteria to enter a state of non-replicating persistence and
which we recently found to be potent inhibitors of MABSC biofilm formation, this application proposes to
determine, for the first time, whether adding a biofilm inhibitor to standard antibiotic regimens may improve
cure. Proof-of-concept of the therapeutic benefit of this approach with clinically-used drugs could be a short
route to the clinic.
Aim 1 will first test the hypothesis that, through its involvement in inducing a state of persistence in response to
hypoxia, the two-component regulator DosRS contributes to the ability of MABSC to form biofilms and develop
phenotypic drug tolerance in a chronic CF (b-ENaC-Tg) mouse model of MABSC infection recently developed
at Colorado State University. Aim 2 will validate DosRS as the bona fide target of the biofilm inhibitors in
MABSC. Finally, Aim 3 will assess the adjunct therapeutic potential of these biofilm inhibitors in MABSC-
infected b-ENaC-Tg mice.

## Key facts

- **NIH application ID:** 10050870
- **Project number:** 1R21AI147326-01A1
- **Recipient organization:** COLORADO STATE UNIVERSITY
- **Principal Investigator:** Mary Jackson
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $228,000
- **Award type:** 1
- **Project period:** 2020-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10050870

## Citation

> US National Institutes of Health, RePORTER application 10050870, Adjunct therapeutic potential of a repurposed drug inhibiting Mycobacterium abscessus biofilm formation (1R21AI147326-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10050870. Licensed CC0.

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