# Effect of Microenvironment on the Activity of Mycobacteriophages for Treating Mycobacterium abscessus

> **NIH NIH R21** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2022 · $194,375

## Abstract

Novel therapies are needed to control the growing problem of antibiotic-resistant bacterial infections.
Bacteriophages (phages) are viruses that infect and kill bacteria. Because phages and antibiotics differ in their
killing mechanisms, phage therapy is a potential strategy for prevention and treatment of drug resistant
bacteria.
Drug resistant nontuberculous mycobacteria (NTM) infections are on the rise and they are a significant threat
for people with underlying lung diseases such as cystic fibrosis (CF), chronic obstructive pulmonary disease
(COPD) or non-CF bronchiectasis. Mycobacterium abscessus is one of the most common NTMs encountered
in pulmonary NTM disease and it is the most difficult to treat. M. abscessus is extremely drug resistant and
there is no systematically proven regimen that is effective. Phage therapy, involving a cocktail of three
mycobacteriophages (mycophages), was recently employed under compassionate use conditions to treat
disseminated M. abscessus disease in a CF patient. This mycophage treatment was associated with clinical
improvement of the patient. However, the M. abscessus infection of the patient has yet to fully resolve and
twice-daily treatment with intravenous mycophages is ongoing two years later. The limitations of the ongoing
mycophage treatment are unknown.
A significant gap in knowledge for phage therapy is whether phages can interact with their host bacteria in the
different microenvironments encountered during infection. M. abscessus is able to both survive intracellularly in
macrophages and extracellularly in biofilms. Whether mycophages can kill M. abscessus in these
environments is unknown. The ability of mycophages to traverse and act in normal mucus or pathological CF
mucus is also unknown. Working with a collection of M. abscessus isolates and mycophages, including those
from the ongoing clinical case, we will evaluate the impact of each of these potential barriers (macrophages,
biofilms, and mucus) on mycophage activity. The results of these studies will shed light on microenvironments
that may limit phage activity for M. abscessus specifically and, more broadly, inform on potential challenges to
phage therapy for intracellular, biofilm forming, and pulmonary bacterial pathogens. We expect the knowledge
gained will drive development of strategies to improve phage therapy as an option to prevent and treat drug
resistant bacterial infections. Given the need for therapies to treat M. abscessus, this R21 is responsive to
NOT-AI-17-016 (Notice of NIAID’s Interest in Biomedical Research in non-AIDS associated, Pulmonary Non-
Tuberculous Mycobacterial (NTM) Infections).

## Key facts

- **NIH application ID:** 10454361
- **Project number:** 5R21AI163677-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Miriam S. Braunstein
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $194,375
- **Award type:** 5
- **Project period:** 2021-07-20 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10454361

## Citation

> US National Institutes of Health, RePORTER application 10454361, Effect of Microenvironment on the Activity of Mycobacteriophages for Treating Mycobacterium abscessus (5R21AI163677-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10454361. Licensed CC0.

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