# Understanding in vivo antibiotic resistance in diverse Pseudomonas aeruginosa populations

> **NIH NIH R01** · GEORGIA INSTITUTE OF TECHNOLOGY · 2021 · $331,650

## Abstract

Summary
Cystic fibrosis (CF) is a genetic disease that results in persistent and chronic lung infections which
reduce lung function over time. Pseudomonas aeruginosa (Pa), an opportunistic bacterial
pathogen that infects patients lungs at a young age and persists throughout life, is a major
contributing factor. Aggressive antibiotic regimes have significantly prolonged the lives of CF
patients, yet Pa populations still dominate during end stage lung disease. Why antibiotic
treatments against Pa ultimately fail remains unclear, but one plausible explanation is that Pa
populations in the CF lung gain higher levels of AMR collectively as they become more
phenotypically and genetically diverse over time. Understanding how Pa population heterogeneity
contributes to antimicrobial resistance (AMR), and how Pa population diversity contributes to the
organism’s survival, are important considerations for the future development of effective
diagnostic and treatment strategies. Understanding of in vivo AMR is limited by a lack of empirical
studies focused on how factors such as evolutionary trade-offs and social interactions between
Pa isolates affect heterogeneity and influence AMR. This study will focus on the impact of intra-
species diversity on AMR using a unique set of Pa strain populations already collected from 50
sputum samples. The main goals are to (i) reveal how the level of heterogeneity in Pa populations
in CF patients determines the extent of AMR; (ii) ascertain evolutionary factors that leads to AMR
heterogeneity; (iii) identify in vivo genomic signatures of AMR using Genome Wide Association
Studies (GWAS). The research described in this project will provide valuable insights into
antimicrobial resistance in chronic CF infection, because it will introduce novel methodology for
antimicrobial susceptibility testing in clinics by taking population dynamics into account. Outcomes
could also lead to new models and platforms for studying the evolution of virulence and AMR in
populations. In the future, the ideas presented here can be further expanded to include studies
on other species important in CF and other polymicrobial communities.

## Key facts

- **NIH application ID:** 10206986
- **Project number:** 1R01AI153116-01A1
- **Recipient organization:** GEORGIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Stephen Paul Diggle
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $331,650
- **Award type:** 1
- **Project period:** 2021-04-09 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10206986

## Citation

> US National Institutes of Health, RePORTER application 10206986, Understanding in vivo antibiotic resistance in diverse Pseudomonas aeruginosa populations (1R01AI153116-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10206986. Licensed CC0.

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