# Antibiotic activities against S. aureus during P. aeruginosa co-infection

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $459,754

## Abstract

Summary Abstract
Predicting the efficacy of an antibiotic in a patient is a critical component of successfully treating infection.
Currently, there is an over-reliance on susceptibility assays involving pure bacterial cultures and controlled
growth conditions. These conditions are drastically different to those experienced by the bacteria during
infection. Hence, these assays fail to account for extrinsic factors that influence antibiotic susceptibility in the
infection environment. This contributes to unacceptable rates of treatment failure. Staphylococcus aureus is
responsible for numerous difficult-to-treat infections and antibiotic treatment failure is common. The
identification of novel extrinsic factors that significantly influence S. aureus antibiotic susceptibility in vivo will
greatly improve our ability to predict antibiotic efficacy in patients, leading to improved treatment outcomes.
These factors may include host interactions, nutrient and oxygen availability and interactions with other
microorganisms during polymicrobial infection.
 Our preliminary studies demonstrate that P. aeruginosa produced molecules dramatically alter S.
aureus antibiotic susceptibility. We find the production of these molecules is highly variable among P.
aeruginosa clinical isolates. Preliminary experiments in mice suggest these interactions play an important role
in determining antibiotic efficacy in vivo.
 We hypothesize that P. aeruginosa strongly influences S. aureus antibiotic susceptibility in patients
during polymicrobial infection.
In Aim 1, we propose to elucidate the molecular mechanisms responsible for this altered antibiotic efficacy.
Elucidation of these mechanisms will improve our understanding of S. aureus antibiotic tolerance and may also
lead to the development of novel adjuvants for the eradication of S. aureus populations.
 In Aim 2, to determine the importance of P. aeruginosa/S. aureus interactions in patients, we will
examine clinical isolate pairs from burn and cystic fibrosis patients.
 In Aim 3, to determine the relevance of these interactions during infection, we will examine antibiotic
efficacy against S. aureus mono-infection and during co-infection with P. aeruginosa using two complimentary
mouse models of infection.
 Together, these experiments promise to reveal the role of bacterial interaction in determining the
outcome of antibiotic treatment of S. aureus. This will facilitate the future development of more sophisticated,
more accurate susceptibility determination and improved treatment outcomes in patients.

## Key facts

- **NIH application ID:** 9836796
- **Project number:** 5R01AI137273-03
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Brian Patrick Conlon
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $459,754
- **Award type:** 5
- **Project period:** 2018-01-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9836796

## Citation

> US National Institutes of Health, RePORTER application 9836796, Antibiotic activities against S. aureus during P. aeruginosa co-infection (5R01AI137273-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9836796. Licensed CC0.

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