Staphylococcus aureus leukocidin ED contributes to systemic infection by targeting neutrophils and promoting bacterial growth in vivo

By Francis Alonzo, M. A. Benson, John Chen, R. Novick, Bo Shopsin, Victor J. Torres. 2011

162 citations recorded by the source corpus.

Bloodstream infection with Staphylococcus aureus is common and can be fatal. However, virulence factors that contribute to lethality in S. aureus bloodstream infection are poorly defined. We discovered that LukED, a commonly overlooked leucotoxin, is critical for S. aureus bloodstream infection in mice. We also determined that LukED promotes S. aureus replication in vivo by directly killing phagocytes recruited to sites of haematogenously seeded tissue. Furthermore, we established that murine neutrophils are the primary target of LukED, as the greater virulence of wild‐type S. aureus compared with a lukED mutant was abrogated by depleting neutrophils. The in vivo toxicity of LukED towards murine phagocytes is unique among S. aureus leucotoxins, implying its crucial role in pathogenesis. Moreover, the tropism of LukED for murine phagocytes highlights the utility of murine models to study LukED pathobiology, including development and testing of strategies to inhibit toxin activity and control bacterial infection.

Subfields: Clinical Biochemistry, Infectious Diseases, Molecular Biology

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Clinical Biochemistry

1. Victor J. Torres
2. Francis Alonzo

In Infectious Diseases

1. Victor J. Torres
2. Francis Alonzo
3. Ashley L. DuMont
4. M. A. Benson

In Molecular Biology

1. Victor J. Torres
2. Francis Alonzo
3. Ashley L. DuMont
4. M. A. Benson

Citations in the corpus

• Disarming Staphylococcus aureus from destroying human cells by simultaneously neutralizing six cytotoxins with two human monoclonal antibodies (2017, background): “aureus leukocidins are highly adapted to the human host and do not elicit appreciable toxicity towards rodent cells with the exception of LukED.(14,15) Since mice and rats are the most commonly used species”
• The Bicomponent Pore-Forming Leucocidins of Staphylococcus aureus (2014, methodology): “aureus strains), it is present in a greater proportion ( 70%) of strains (47, 95).”
• Staphylococcus aureus Elaborates Leukocidin AB To Mediate Escape from within Human Neutrophils (2013, background): “aureus pathogenicity island 1 (SaPI1) site (20).”