# The Impact of the Cystic Fibrosis infection environment on biofilm development of nontuberculous mycobacteria

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $391,237

## Abstract

Project Summary/Abstract -- DePas
The emergence of nontuberculous mycobacteria (NTM) as dangerous, antibiotic resistant pulmonary
pathogens is outpacing research into their mechanisms of pathogenesis. Our long-term goal is to characterize
NTM in the infection environment and develop new therapeutic approaches aimed at specific in vivo bacterial
activities. The objective of this proposal is to directly assess NTM biofilm formation and growth rate in situ and
determine how the infection environment impacts these processes. We hypothesize that the spatial and
chemical environment of sputum from people with Cystic Fibrosis (CF) sputum supports the formation of
antibiotic tolerant, slow-growing NTM biofilms through regulated cellular processes. The rationale for this
proposal is that the biofilm state and growth rate of a specific bacterial pathogen can have drastic influences on
the efficacy of antibiotics and the host immune response. We will test our central hypothesis with two specific
aims: 1) Determine how NTM biofilm formation is regulated by the CF chemical environment and how it
impacts antibiotic tolerance and 2) Determine how anoxia-induced dormancy influences physiological tolerance
and biofilm formation of NTM. The proposed work will combine three innovative complementary techniques
into one coherent strategy for investigating infection-relevant phenotypes such as biofilm formation and
dormancy. We will employ a novel tissue clearing/bacterial visualization technique MiPACT-HCR in both aims.
In Aim 2, we will also utilize a 3D model of the CF infection environment, the Agar Block Biofilm Assay. We will
use a new in vitro aggregation assay that allows us to track and quantify the transition from planktonic cells to
biofilms in both Aims. The proposal is significant because it will provide an accurate description of the
physiological state of NTM during human infection to inform antibiotic choice and dosage decisions. It is also
significant in that it will provide molecular targets for development of anti-biofilm and anti-dormancy strategies
against NTM. The expected outcome of this work is a thorough understanding of the structure and prevalence
of NTM communities during infection of patients with CF and insight into the mechanistic pathways driving
biofilm formation and dormancy. These results will have a positive impact by assisting physicians make more
appropriate treatment choices for NTM infections.

## Key facts

- **NIH application ID:** 10800755
- **Project number:** 5R01AI170607-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** William H. DePas
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $391,237
- **Award type:** 5
- **Project period:** 2023-03-03 → 2028-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10800755

## Citation

> US National Institutes of Health, RePORTER application 10800755, The Impact of the Cystic Fibrosis infection environment on biofilm development of nontuberculous mycobacteria (5R01AI170607-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10800755. Licensed CC0.

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