# Mechanistic Studies Of The Staphylococcus aureus LukAB Cytotoxin

> **NIH NIH R01** · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · 2024 · $637,453

## Abstract

PROJECT SUMMARY/ABSTRACT
Staphylococcus aureus is responsible for many hospital- and community-associated infections worldwide.
However, therapeutic options to combat these infections are limited due to the high level of antibiotic resistance
and lack of effective vaccines. Thus, there is a significant need for the development of effective therapeutics
against this bacterium. Critical to the pathogenesis of S. aureus is the killing of phagocytes, innate immune cells
integral to the control of Staphylococcal infections. The long-term goal of this research program is to understand
the mechanism employed by S. aureus to injure these critical immune cells. We have discovered that the
leukocidin A/B (LukAB) plays an essential role in protecting S. aureus from phagocyte-mediated killing by
targeting and eliminating these cells. LukAB is chromosomally encoded and found in most clinical strains yet is
the most divergent pore-forming toxin. LukAB: is responsible for S. aureus-mediated demise of primary human
phagocytes during ex vivo infections; binds host proteins CD11b and HVCN1; exhibits species specificity by
preferentially targeting the human CD11b and HVCN1 over the murine proteins; is produced in vivo during both
murine and human infections; and is responsible for killing human leukocytes from both the extracellular milieu
as well as intracellularly in the phagosome when produced by S. aureus. The primary goals of this competitive
renewal application are to: define the molecular mechanism(s) by which LukAB kills human phagocytes (Aim 1),
disentangle the regulatory network involved in lukAB expression (Aim 2), and delineate the contribution of LukAB
to S. aureus pathogenesis in vivo (Aim 3). To accomplish these Aims, we will employ a multidisciplinary approach
that combines techniques from bacteriology, biochemistry, cell biology, immunology, and pathogenesis, together
with ex vivo and in vivo infection models. Completion of these studies will provide much needed fundamental
insight into how LukAB contributes to the pathogenesis of S. aureus.

## Key facts

- **NIH application ID:** 10801351
- **Project number:** 2R01AI099394-10
- **Recipient organization:** ST. JUDE CHILDREN'S RESEARCH HOSPITAL
- **Principal Investigator:** Victor J. Torres
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $637,453
- **Award type:** 2
- **Project period:** 2013-06-04 → 2028-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10801351

## Citation

> US National Institutes of Health, RePORTER application 10801351, Mechanistic Studies Of The Staphylococcus aureus LukAB Cytotoxin (2R01AI099394-10). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10801351. Licensed CC0.

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