# Staphylococcus aureus Survival During Nutrient Restriction and Suppression of Host Immunity.

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2024 · $459,189

## Abstract

Project Summary
Staphylococcus aureus (Sa) is a leading cause of nosocomial infection in the United States and is a predominant
pathogen in communities. Treatment of Sa infections is complicated by the prevalence of antibiotic resistant and
highly virulent clones, making new therapeutic alternatives a necessity. Sa survives during infection by
subverting immune defenses and adapting to host-imposed nutrient restriction. Yet, we lack a unifying
understanding of these adaptations to the host environment, which complicates the development of new
therapeutics and vaccines. We recently discovered that a cofactor required for metabolic enzyme complex
function and potent antioxidant, lipoic acid (LA), is a critical mediator of Sa growth and survival during infection.
Furthermore, we found that Sa releases the lipoylated E2 subunit of the metabolic enzyme complex pyruvate
dehydrogenase to blunt protective innate immune responses via its LA moiety. Thus, our work has uncovered a
mechanism of Sa survival during infection that links bacterial metabolism and nutrient acquisition to defense
against innate immunity. Despite establishing these roles for LA biosynthesis and salvage in Sa pathobiology,
there exist major gaps in our understanding of the mechanics of how LA blunts immunity and promotes optimal
metabolism during infection. Notably: (i) the precise mechanism by which bacterial LA-protein blunts immune
activation has not been elucidated; (ii) regulation of LA distribution on essential metabolic enzymes is not
understood; (iii) the role of LA in mediating defense against oxidative stress has not been investigated; and (iv)
the relevance of LA acquisition to survival in different infection sites is not understood. This renewal application
will address these gaps in knowledge by ascertaining precisely how LA subverts immunity and the mechanics of
LA synthesis/salvage that promote bacterial survival in vivo with the potential to lay the groundwork for new
targeted therapeutics. Aim 1 will determine how bacterial-derived LA blunts immune responses. Aim 2 will
determine how Sa regulates LA salvage and distribution. Aim 3 will investigate how accessibility to host nutrients
in different tissues determines the requirement for LA during infection.

## Key facts

- **NIH application ID:** 10811701
- **Project number:** 5R01AI120994-10
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Francis Alonzo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $459,189
- **Award type:** 5
- **Project period:** 2016-01-15 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10811701

## Citation

> US National Institutes of Health, RePORTER application 10811701, Staphylococcus aureus Survival During Nutrient Restriction and Suppression of Host Immunity. (5R01AI120994-10). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10811701. Licensed CC0.

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