# Staphylococcus aureus and Pseudomonas aeruginosa interactions in wound pathogenesis

> **NIH NIH R21** · UNIVERSITY OF COLORADO DENVER · 2022 · $187,293

## Abstract

PROJECT ABSTRACT
Patients with chronic wound infections have a rich microbial community and several bacterial species have been
identified as the main drivers of persistent disease. Two of the most prominent wound pathogens are
Staphylococcus aureus (including methicillin-resistant S. aureus (MRSA)), and Pseudomonas aeruginosa. The
SENTRY antimicrobial surveillance program identified S.
three
11%,
aureus P. aeruginosa and Enterococcus spp. as the
 main pathogens causing skin and soft tissue infections (SSTI) in the United States accounting for 44%,
 and 9% of all SSTI during the years 1998 and 2004.
, ,
Chronic leg ulcers (CLUs) affect 1-2% of people
worldwide, are a major cause of prolonged morbidity and have a high recurrence rate. S. aureus and P.
aeruginosa are the most common agents isolated from CLUs usually as biofilm resistant to antibiotic therapy.
Biofilms are notoriously difficult to eradicate, due to their recalcitrance to antibiotics and ability to evade clearance
by the immune system. There is evidence that these two pathogens can exchange specialized metabolites that
have the potential to alter cellular behavior and lead to community-wide antibiotic tolerance. Specifically, in vitro
co-cultivation studies with S. aureus increased Pseudomonas quinolone gene expression that regulates the
expression of several quorum-sensing dependent P. aeruginosa virulence factors and iron acquisition systems.
As the prevalence of MRSA increases in the US, new strategies are necessary to treat chronic and recurrent
infections. Therefore, the long-term goal is to develop alternative treatment options for chronic wound patients
infected by S. aureus and P. aeruginosa. The objective of this proposal is to determine the biological
consequences of MRSA modification of P. aeruginosa pyochelin. The rationale underlying this proposal is our
preliminary findings that S. aureus and P. aeruginosa act synergistically, which may in part explain why co-
infections with these two pathogens lead to worse outcomes. In preliminary imaging mass spectrometry studies,
we determined that a novel methylated pyochelin derivative is produced during the interaction of MRSA and P.
aeruginosa. We identified the MRSA gene responsible and we can detect this new metabolite in a mouse wound
infection model. Our initial studies confirm that the pyochelin originates from P. aeruginosa and then is
enzymatically converted by MRSA into a new methylated form. We hypothesize that MRSA methylates
pyochelin to compete in a polymicrobial environment. In order to test this hypothesis we will (i) characterize
methylated pyochelin generated by MRSA through biochemical, genetic and infection modeling methods and;
(ii) determine the functional consequences of methylated pyochelin on P. aeruginosa physiology and
pathogenesis. The expected outcomes of this work will increase our understanding the biosynthesis and
biological activities of specialized metabolites that drive inter-species interaction...

## Key facts

- **NIH application ID:** 10531680
- **Project number:** 1R21AI166805-01A1
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** ALEXANDER R HORSWILL
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $187,293
- **Award type:** 1
- **Project period:** 2022-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10531680

## Citation

> US National Institutes of Health, RePORTER application 10531680, Staphylococcus aureus and Pseudomonas aeruginosa interactions in wound pathogenesis (1R21AI166805-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10531680. Licensed CC0.

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