# Molecular mechanisms of inherent drug resistance in non-tuberculous mycobacteria

> **NIH NIH R01** · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · 2024 · $768,176

## Abstract

Abstract
Infections caused by non-tuberculous mycobacteria (NTMs) are substantial clinical problems. The response to
therapy is disappointing and the goal for patients with chronic infections is generally to control rather than cure
infection. This means extended antibiotic treatment with drugs and associated toxicities that tend to accumulate
over time. While there has been considerable investment in developing new antibiotics for the treatment of
tuberculosis, caused by the related organism Mycobacterium tuberculosis (Mtb), most of these emergent
therapies have little or no activity in NTMs. This has made treatment of the rising number of NTM cases highly
problematic. Here we propose to use tools we have recently developed to study NTMs and identify mechanisms
to resensitize these pathogens to antibiotics to which they are intrinsically resistant. We will use a new tissue
culture model of lung infection together with genetic approaches to find and validate genes and pathways that
allow growth inhibition at achievable drug concentrations and/or more rapid killing by existing drugs and
advanced antibacterial compounds in Mycobacterium abscessus. We will then explore the underlying biologic
mechanisms of sensitization and extend these observations to an even more common cause of human infection,
organisms of the Mycobacterium avium complex. Our goal is to determine the therapeutic targets that will best
result in bacterial clearance even in the absence of effective host defenses.

## Key facts

- **NIH application ID:** 10932891
- **Project number:** 5R01AI179642-02
- **Recipient organization:** HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH
- **Principal Investigator:** Jeremy Michael Rock
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $768,176
- **Award type:** 5
- **Project period:** 2023-09-22 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10932891

## Citation

> US National Institutes of Health, RePORTER application 10932891, Molecular mechanisms of inherent drug resistance in non-tuberculous mycobacteria (5R01AI179642-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10932891. Licensed CC0.

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