# Impacts of host lipid composition on antimicrobial susceptibilities of Staphylococcus aureus

> **NIH NIH R01** · UNIVERSITY OF GEORGIA · 2024 · $457,744

## Abstract

Although the CDC's 2019 report on Antibiotic Resistance Threats in U.S. shows that methicillin-resistant
Staphylococcus aureus (MRSA) cases have declined, nearly 85% of all deaths attributed to antibiotic resistance
between 2005 and 2016 were the result of MRSA infections. Bloodstream infections from community-acquired
MRSA have declined less sharply than hospital-acquired MRSA during this time (-17% and -6.9%, respectively),
whereas cases of community-associated methicillin-susceptible S. aureus (MSSA) have risen nearly 4%. Nearly
half of all health-care-associated infections are now attributed to MSSA rather than MRSA. At the same time,
MSSA and MRSA are being identified as the cause of infective endocarditis with greater frequency. The changing
dynamics of S. aureus infections demonstrate the critical need to better our understanding of its pathogenesis
in order to develop new approaches for prevention and treatment. One of the competitive advantages S. aureus
has within the infection site is its ability to scavenge host-derived fatty acids to satisfy its own lipid biosynthesis
needs. The mechanisms of the fatty acid kinase pathway are well-documented for monounsaturated fatty acids
like oleic acid. However, the fatty acid content of the human body varies dramatically between different organs
and tissues. Despite their prevalence in the human body, we have overlooked the role of host-derived saturated,
straight-chain fatty acids (SCFAs) in investigations of the fatty acid kinase pathway. Our long-term goal is to
increase the efficacy of existing antibacterial therapies by purposefully and selectively remodeling the
staphylococcal membrane during infection. The overall objective for this application is to define the lipid
composition of S. aureus within the complex environment of the mammalian host and identify the impacts of
host-derived FAs on the antimicrobial susceptibilities of S. aureus. Our central hypothesis is that the S. aureus
membrane mimics the fatty acyl composition of the infection site to a greater extent than previously thought and
that the resulting impacts on membrane physiology modify the tolerance of S. aureus to antimicrobials. The
rationale for this project is that more effective antimicrobial treatment regimens will be developed by accounting
for or exploiting the lipid composition of S. aureus when residing within the mammalian host. In Aim 1, we will
determine the prevalence and fate of mammalian-derived saturated and unsaturated fatty acids using advanced
liquid chromatography-mass spectrometry-based lipidomics. In Aim 2, we will identify the impact of S. aureus'
use of exogenous fatty acids on its membrane physiology and cell morphology. In Aim 3, we will test the
hypothesis that host-derived fatty acids can influence antibiotic tolerances of S. aureus in vitro and in vivo. We
expect that the results of our research will prompt greater appreciation and consideration of host-derived fatty
acids as modulators of antibi...

## Key facts

- **NIH application ID:** 10754572
- **Project number:** 5R01AI173144-02
- **Recipient organization:** UNIVERSITY OF GEORGIA
- **Principal Investigator:** Kelly M. Hines
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $457,744
- **Award type:** 5
- **Project period:** 2022-12-14 → 2027-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10754572

## Citation

> US National Institutes of Health, RePORTER application 10754572, Impacts of host lipid composition on antimicrobial susceptibilities of Staphylococcus aureus (5R01AI173144-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10754572. Licensed CC0.

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