# Screening phage-host receptor interactions using thermal proteome profiling

> **NIH NIH P20** · UNIVERSITY OF KANSAS LAWRENCE · 2022 · $211,900

## Abstract

The long-term goal of this work is to correlate environmental reservoirs of pathogenic NTM, mine reservoirs 
for NTM-specific mycobacteriophages from correlated environments, and develop a high-throughput tool to 
interrogate mycobacteriophage-NTM interactions. The overall objective of this proposal is to increase the 
discovery rate of new NTM molecular targets of mycobacteriophages to advance novel therapeutics, 
including phage-based treatments. The focus in this proposal is on Mycobacterium abscessus (MABS). While 
MABS is the second most common cause of pulmonary infections in the U.S., MABS infections may have 
higher rates of adverse patient outcomes compared to more common NTM pathogens. The hypothesis of 
this study is MABS-specific mycobacteriophages sourced from MABS-rich samples can be used to identify 
novel, phage-based molecular targets for treatment or removal of MABS. The rationale for this project is that 
the development of MABS-specific mycobacteriophage tools will contribute to quantitative MABS risk 
assessments and promote alternative treatment strategies for antibiotic-resistant MABS. 
To achieve the objectives of this proposal and test our hypothesis, we will correlate MABS-rich 
environments based on abundance and genetic similarity to pathogenic MABS strains using high-throughput 
sequencing data of environmental, human sputum, and clinically isolated samples. Novel, high throughput 
sequencing tools are required to capture spatial and temporal variation in MABS subspecies resolution, 
presence, and abundance. We will achieve this by employing multilocus, metabarcoding of 16S rRNA, rpoB, 
hsp65, and erm(41). Once environmental MABS reservoirs have been correlated, highly ranked 
environments will be mined for MABS-specific bacteriophages. Interactions between these 
mycobacteriophages and NTM organisms will be screened to identify novel NTM-molecular targets using 
thermal proteome profiling. The corresponding mycobacteriophage proteins and previously published reports 
for mycobacteriophage proteins with NTM affinity will be used to quantify binding efficiency and determine 
lysis from without potential. 
Results from this study can inform immunocompromised patient behavior to avoid high-risk NTM reservoirs 
and determine if high-throughput sequencing techniques can be applied for species-level resolution of MABS 
in human sputum. The development of a high-throughput phage/host-protein screening platform would 
accelerate the identification of phage molecular targets, a potential source for the development of novel NTM 
antimicrobials.

## Key facts

- **NIH application ID:** 10661882
- **Project number:** 5P20GM113117-07
- **Recipient organization:** UNIVERSITY OF KANSAS LAWRENCE
- **Principal Investigator:** Justin Michael Hutchison
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $211,900
- **Award type:** 5
- **Project period:** 2021-10-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10661882

## Citation

> US National Institutes of Health, RePORTER application 10661882, Screening phage-host receptor interactions using thermal proteome profiling (5P20GM113117-07). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10661882. Licensed CC0.

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