# Contribution of LukED to Staphylococcus aureus pathobiology

> **NIH NIH R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2021 · $517,850

## Abstract

PROJECT SUMMARY
Staphylococcus aureus is responsible for a large number of hospital- and community-acquired infections
worldwide. The rise in the incidence of S. aureus infections is primarily due to a combination of increased
antibiotic resistance and augmented virulence of strains associated with community infections. In the absence
of a protective vaccine, studies aimed at dissecting virulence strategies of S. aureus are desperately needed
with the hope of identifying novel targets for the generation of new treatments to combat this pathogen. An
important pathogenic strategy of S. aureus is the production of exotoxins that target and kill host cells. Among
these, S. aureus strains associated with human infections can produce up to five different pore-forming bi-
component toxins known as leukocidins. The long-term objective of our program is to understand the molecular
details by which these leukocidins influence the pathophysiology of S. aureus infection through targeting cells of
the immune system. The present application focuses on one of these toxins as a model leukocidin, leukocidin
ED (LukED). The importance of the proposed research originates from our recent discoveries that LukED: (i) is
a critical virulence factor involved in the lethality of mice upon S. aureus bloodstream infection, (ii) is required for
promoting bacterial replication in vivo, (iii) contributes to S. aureus pathogenesis by targeting and killing immune
cells in vivo, and (iv) targets a wide array of host cells in a receptor-dependent manner. The goals of this research
program are to understand the mechanisms by which LukED targets its different host receptors, to define the
details by which LukED injures endothelial cells to promote the lethality associated with bloodstream infection,
and to elucidate how LukED interacts with the other leukocidins to modulate pathogenesis. To this end, we
propose to employ a multidisciplinary approach that combines toxin-receptor biochemical studies with primary
human cell biology and novel murine models of infection. The data gathered from these studies will provide much
needed insight into the molecular details of how the bi-component leukocidins contribute to S. aureus
pathobiology.

## Key facts

- **NIH application ID:** 10214497
- **Project number:** 5R01AI105129-08
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Victor J. Torres
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $517,850
- **Award type:** 5
- **Project period:** 2013-12-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10214497

## Citation

> US National Institutes of Health, RePORTER application 10214497, Contribution of LukED to Staphylococcus aureus pathobiology (5R01AI105129-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10214497. Licensed CC0.

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