# Examination of phage resistance and susceptibility in M tuberculosis

> **NIH NIH R21** · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · 2024 · $228,750

## Abstract

Much is unknown of mechanisms of bacteriophage resistance and susceptibility in
Mycobacterium tuberculosis (Mtb) and are still unsolved. Studies have provided useful
classification schemes, such as whole genome sequencing and spoligo typing using DNA
sequences. Unfortunately, DNA sequencing has not provided a clear understanding or basis for
explaining the biology of phage typing or phage/host interactions in Mycobacterium tuberculosis
at a time when phage therapy may provide a possible solution to treatment in the face of the
ongoing problem of the worldwide drug resistant epidemic in tuberculosis. Bacteriophages have
the potential to provide a new molecular approach for treating drug-resistant tuberculosis.
However, in order to develop these effective phage therapies, we need to better understand the
biology of phage-host interactions in Mtb.
In this study, we propose to examine phage-host interactions using an established stock of
phages from decades-old archived collection of Mtb phages. This will be accomplished through
three specific aims: 1) Determine the similarities and differences that determine phage host
range. We will characterize the distinctive properties of these phages by their host range
limitations, morphological and DNA sequencing differences and similarities, and phage
attachment properties. 2) Identify CRISPR sites within the host genome that confer immunity.
We will concentrate on host properties by searching for novel restriction enzymes, receptors
and CRISPR sites that maybe associated with phage resistance. 3) Evaluate how host lineages
impact susceptibility/resistance to phage. We will compare the phages to Mtb host genome
sequences among and within well-established lineages to look for patterns of phage interaction.
Our findings have the potential to establish a new understanding of phage-host interactions in
Mtb. This knowledge will be used to ultimately develop new directions for phage-based
therapies to treat drug-resistant tuberculosis.

## Key facts

- **NIH application ID:** 10952675
- **Project number:** 1R21AI185823-01
- **Recipient organization:** TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
- **Principal Investigator:** Jeffrey D. Cirillo
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $228,750
- **Award type:** 1
- **Project period:** 2024-05-23 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10952675

## Citation

> US National Institutes of Health, RePORTER application 10952675, Examination of phage resistance and susceptibility in M tuberculosis (1R21AI185823-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10952675. Licensed CC0.

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