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Staphylococcus Aureus Leucocidin ED Contributes to Systemic Infection by Targeting Neutrophils and Promoting Bacterial Growth in Vivo

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Journal Mol Microbiol
Date 2011 Dec 7
PMID 22142035
Citations 104
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Abstract

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.

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References
1.
Bodey G, Buckley M, SATHE Y, Freireich E . Quantitative relationships between circulating leukocytes and infection in patients with acute leukemia. Ann Intern Med. 1966; 64(2):328-40. DOI: 10.7326/0003-4819-64-2-328. View

2.
McNamara P, Khalili S, Proctor R . Identification, cloning, and initial characterization of rot, a locus encoding a regulator of virulence factor expression in Staphylococcus aureus. J Bacteriol. 2000; 182(11):3197-203. PMC: 94507. DOI: 10.1128/JB.182.11.3197-3203.2000. View

3.
Voyich J, Braughton K, Sturdevant D, Whitney A, Said-Salim B, Porcella S . Insights into mechanisms used by Staphylococcus aureus to avoid destruction by human neutrophils. J Immunol. 2005; 175(6):3907-19. DOI: 10.4049/jimmunol.175.6.3907. View

4.
Geisinger E, Adhikari R, Jin R, Ross H, Novick R . Inhibition of rot translation by RNAIII, a key feature of agr function. Mol Microbiol. 2006; 61(4):1038-48. DOI: 10.1111/j.1365-2958.2006.05292.x. View

5.
Labandeira-Rey M, Couzon F, Boisset S, Brown E, Bes M, Benito Y . Staphylococcus aureus Panton-Valentine leukocidin causes necrotizing pneumonia. Science. 2007; 315(5815):1130-3. DOI: 10.1126/science.1137165. View