# Bacteriophage as a predictive biomarker in chronic Pseudomonas airway disease

> **NIH NIH K23** · CHILDREN'S HOSPITAL OF LOS ANGELES · 2023 · $199,044

## Abstract

PROJECT SUMMARY / ABSTRACT
 Despite major advances in therapy, pulmonary disease continues to dominate the clinical course
of patients with cystic fibrosis (CF). All patients with CF develop chronic lung infections, with
Pseudomonas aeruginosa (Pa) becoming a predominant organism in adulthood. Even in the face of
chronic inhalational antibiotic therapy to target Pa in the lungs, CF patients experience intermittent
pulmonary exacerbations with stepwise decline in lung function leading to eventual respiratory failure.
Novel treatment strategies are urgently needed to address the damaging effects of chronic Pa in the
lungs of CF patients. This will allow for all patients with CF to fully benefit of an evolving therapeutic
landscape to address their defective CF gene function.
 I discovered the presence of the Pa filamentous (Pf) bacteriophage, in cohorts of patients with CF
in Stanford and Denmark. Pf was associated with chronicity of Pa and more severe exacerbations
(Burgener et al, Science Translational Medicine 2019). This constituted the first demonstration of the
involvement of bacteriophage in human lung disease. This proposal aims to delve into the mechanisms
behind these associations. Given the known shortcomings of chronic inhalational antibiotic therapy, I
will test the hypothesis that in the lung Pf provides antibiotic tolerance and is a predictive biomarker to
guide in choosing effective inhalational therapeutics. The first aim utilizes banked respiratory Pa
isolates to (1a), assess antibiotic tolerance under conditions present in the lung, (1b) perform whole
genome sequencing to assess for presence of antibiotic resistance genes and (1c) perform evolutionary
experiments to investigate acquisition of resistance as a function of Pf. The second aim will assess Pf
as a lung disease predictive biomarker in (2a) a retrospective cohort evaluating response to
exacerbations therapy and (2b) perform a cross-over clinical trial to assess for differential effects of Pf
on lung function. This proposal, supported by exciting and novel preliminary data, promises to provide
rationale and mechanistic foundation for Pf to be used as a predictive biomarker to guide inhalational
antibiotic choices in CF airway disease management.
 The proposed research draws upon my prior experience in clinical pulmonary medicine and
growing expertise in translational research. Along with my mentors and advisory committee, I present
a comprehensive career development plan for didactics and technical training in microbiology,
genomics, and clinical trial design and biostatistics. This training, along with the clinical studies and
experiments outlined, will allow me to develop skills crucial for my transition to an independent
translational research career focused on bringing new therapies and treatment strategies for
transformative management of CF lung disease.

## Key facts

- **NIH application ID:** 10723956
- **Project number:** 1K23HL169902-01
- **Recipient organization:** CHILDREN'S HOSPITAL OF LOS ANGELES
- **Principal Investigator:** Elizabeth Bendig Burgener
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $199,044
- **Award type:** 1
- **Project period:** 2023-08-22 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10723956

## Citation

> US National Institutes of Health, RePORTER application 10723956, Bacteriophage as a predictive biomarker in chronic Pseudomonas airway disease (1K23HL169902-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10723956. Licensed CC0.

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