# Phage resistance in Mycobacterium tuberculosis

> **NIH NIH R21** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $207,225

## Abstract

Tuberculosis remains a global health threat killing over 1.6 million people annually. Antibiotic
treatment for drug-sensitive infections requires three antibiotics for a minimum of six months,
and resistance to these antibiotics is common. Newly developed drugs are helpful for treating
these resistant infections, but their longevity is challenged by the expectation of further
resistances emerging. Tuberculosis is a potential target for therapeutic treatment with
bacteriophages, which could be used to treat MDR-TB, XDR-TB, and TDR-TB infections, to
shorten standard antibiotic therapy, to reduce the emergence of new resistant strains, to protect
and extend the utility of newly developed antibiotics, and potentially to interfere with
Mycobacterium tuberculosis transmission. Although phage therapy of TB may face substantial
challenges – especially regarding access to the bacterial targets – encouragement is provided
by a successful case study in treating a young Cystic Fibrosis patient with a highly antibiotic
Mycobacterium abscessus infection. Moreover, the limited genetic variability of M. tuberculosis
relative to other bacterial pathogens and preliminary data defining a set of potentially useful
mycobacteriophages for treatment, sets the stage for clinical trials to determine if this is an
effective and safe strategy for TB control. However, an important puzzle-piece is missing.
Currently we know little about the mechanisms of M. tuberculosis resistance to the phages, the
orthogonality of shared resistance profiles, or the impact of resistance mutations on virulence or
antibiotic susceptibility. Without this, compiling therapeutic phage cocktails relies on guessing
which phages are compatible based on genomic diversity, which may correlate only poorly with
resistance and co-resistance profiles. Moreover, understanding the genetic basis of resistance
provides much needed information required to monitor resistance development during phage
therapy trials. Finally, the finding that resistance may commonly inhibit post-DNA injection
events suggests that many resistance mechanisms can be thwarted by use of recombinant
phages carrying counter-defense genes.

## Key facts

- **NIH application ID:** 10129484
- **Project number:** 1R21AI156791-01
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Graham F. Hatfull
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $207,225
- **Award type:** 1
- **Project period:** 2020-12-07 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10129484

## Citation

> US National Institutes of Health, RePORTER application 10129484, Phage resistance in Mycobacterium tuberculosis (1R21AI156791-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10129484. Licensed CC0.

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