# Application of palmitoleic acid to potentiate antibiotic efficacy

> **NIH NIH R21** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2024 · $233,250

## Abstract

Complicated skin and skin structure infections (cSSSIs) including abscesses, burn infections, cellulitis
and diabetic foot infections represent an enormous burden on the healthcare industry. Treatment options are
limited, and treatment failure is common, frequently leading to chronic wound infection. Staphylococcus aureus
is the most common cause of these infections, followed by Enterococcus faecalis.
 Vancomycin, a lipid II targeting antibiotic that inhibits cell wall synthesis, is essential in the treatment of
cSSSI. However, vancomycin-intermediate resistant S. aureus (VISA) and vancomycin-resistant Enterococci
(VRE) are a growing problem. Additionally, even in susceptible populations, antibiotic tolerant persister cells can
survive vancomycin exposure, making eradication of infection difficult to achieve. Identifying ways to increase
the efficacy of vancomycin, to target persister cells and overcome resistance would greatly improve the treatment
of cSSSIs.
 We find that palmitoleic acid, a non-toxic unsaturated fatty acid found in human serum potentiates
vancomycin efficacy against S. aureus and E. faecalis. Strikingly, palmitoleic acid also rapidly sensitizes persister
cells and resistant populations to vancomycin. Vancomycin causes accumulation of the hydrophobic lipid II
molecule at the septum. Our preliminary data suggests that palmitoleic acid is recruited to these hydrophobic
regions which destabilize the membrane and cause cell death. Vancomycin-resistant isolates induce expression
of resistance genes when they encounter vancomycin. We hypothesize that the rapidity of palmitoleic acid-
vancomycin killing may outpace the induction of resistance gene expression, resulting in death of the resistant
strains.
 In this proposal, we will 1) determine how palmitoleic acid/vancomycin kills persister cells and
overcomes vancomycin-resistance and 2) evaluate the efficacy of this therapeutic combination in a pre-clinical
diabetic wound infection model. Utilizing host-produced unsaturated fatty acids to potentiate vancomycin killing
against resistant organisms is conceptually innovative. If successful, this proposal will represent the first steps
toward the development of a powerful therapeutic combination for the eradication of recalcitrant gram-positive
wound infection.

## Key facts

- **NIH application ID:** 10786582
- **Project number:** 1R21AI180407-01
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Sarah Elizabeth Rowe
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $233,250
- **Award type:** 1
- **Project period:** 2024-06-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10786582

## Citation

> US National Institutes of Health, RePORTER application 10786582, Application of palmitoleic acid to potentiate antibiotic efficacy (1R21AI180407-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10786582. Licensed CC0.

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