# Bacterial lipases and adaptation to the host lipid environment

> **NIH AI R01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2026 · $736,822

## Abstract

Project Summary
The host lipid environment is a well-described barrier to bacterial infection at several sites including the skin,
lung, and upper airways. In addition, both bacterial and host lipids serve as signals that promote inflammation.
Bacterial lipids activate Toll-like receptors which initiates cytokine production, immune cell recruitment, and
induction of oxidative burst to control infection. Several pathogenic bacteria evade these lipid-mediated defenses
by secreting lipolytic enzymes (lipases). Bacterial lipases can cause host membrane dissolution, facilitate escape
from cellular compartments, disrupt physical barriers, detoxify antimicrobial lipids, and release nutrient fatty
acids. Despite these established contributions of lipases to infection there exist critical gaps in knowledge on
how lipases drive host immunity and physiology. This is especially true for Staphylococcus aureus which
produces three lipases that have long been presumed to promote virulence, despite scant mechanistic studies.
Recent work from our lab started to fill this gap by providing evidence for a direct role for lipases in immune
evasion and nutrient acquisition during infection. We made the unexpected observation that the S. aureus
secreted lipase, Geh, inhibited activation of innate immune cells in culture. Further, Geh blunted pro-inflammatory
cytokine production during infection and was responsible for bacterial persistence in some tissues but not others,
highlighting tissue-specific contributions of Geh to survival. The blunted cytokine response was not due to direct
functions of Geh on mammalian cells, but rather a result of inactivation of S. aureus lipoproteins, a major
pathogen-associated molecular pattern (PAMP) of Gram-positive bacteria, via ester hydrolysis. While our studies
indicate S. aureus uses lipases to inactivate lipoprotein PAMPs containing saturated straight and branched chain
fatty acids that it synthesizes de novo, it can also acquire host unsaturated f

## Key facts

- **NIH application ID:** 11310533
- **Project number:** 1R01AI191355-01A1
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Francis  Alonzo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** AI
- **Fiscal year:** 2026
- **Award amount:** $736,822
- **Award type:** 1
- **Project period:** 2026-02-01T00:00:00 → 2031-01-31T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11310533

## Citation

> US National Institutes of Health, RePORTER application 11310533, Bacterial lipases and adaptation to the host lipid environment (1R01AI191355-01A1). Retrieved via AI Analytics 2026-07-15 from https://api.ai-analytics.org/grant/nih/11310533. Licensed CC0.

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