# Evaluating Mycobacterium avium glycopeptidolipids as key factors in the transition from biofilm to macrophages

> **NIH NIH R21** · UNIVERSITY OF NOTRE DAME · 2022 · $234,750

## Abstract

Project summary
Non-tuberculosis mycobacteria like M. avium are widespread environmental organisms,
occurring in many habitats, both natural and engineered (). The ability of M. avium to colonize
household plumbing, hot tubs, and garden soils, often places them in close proximity with
humans. Most cases of disease caused by M. avium are pulmonary and the patient population
includes individuals who are elderly, immune-compromised, or have preexisting lung damage
due to an underlying respiratory disease (). Cases of M. avium disease have continued to rise,
with cases increasing an estimated 5-10% annually in the United States (). M. avium pulmonary
disease is both difficult to diagnose and treat. Once diagnosed, treatment with multiple
antibiotics can last 18-24 months, with clinical guidelines indicating continuous treatment for 12
months after the infecting bacteria are no longer detected in patient sputum. Even with this
extended treatment course, recurrence of infection is still common.
M. avium is an intracellular pathogen with macrophages being the primary host cell. Therefore
for the infection to be successful, the mycobacteria must adjust from living in its natural reservoir
within a biofilm to invading and replicating in a macrophage. We know very little about how the
mycobacteria makes this critical transition. We hypothesize that modifications of
glycopeptidolipids, which are major cell surface molecules of M. avium, play a critical role in this
transition and evidence showing their importance in biofilm formation and macrophage
activation supports this argument. In Specific aim 1 we will test this hypothesis by isolating,
from biofilm and macrophages, the different M. avium GPL species and characterize their ability
to modulate macrophage function. We will also generate gene knockouts to produce GPL
mutants and evaluate the M. avium mutants for biofilm formation and macrophage
invasion/survival to define what GPL species are necessary for the observed phenotypes. In
aim 2 we will perform a transcriptional analysis of M. avium grown in broth culture, biofilms and
macrophages to define expression levels of the different genes involved in producing the
various GPLs variants. The transcriptional analysis will have the added benefit of defining more
globally, changes in gene expression which occur as the M. avium transitions from growth in
biofilm to replication in macrophages.

## Key facts

- **NIH application ID:** 10429772
- **Project number:** 1R21AI168662-01
- **Recipient organization:** UNIVERSITY OF NOTRE DAME
- **Principal Investigator:** JEFFREY Scott SCHOREY
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $234,750
- **Award type:** 1
- **Project period:** 2022-03-02 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10429772

## Citation

> US National Institutes of Health, RePORTER application 10429772, Evaluating Mycobacterium avium glycopeptidolipids as key factors in the transition from biofilm to macrophages (1R21AI168662-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10429772. Licensed CC0.

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