Identification of LukPQ, a novel, equid-adapted leukocidin of Staphylococcus aureus.

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Koop, Gerrit 
Vrieling, Manouk 
Storisteanu, Daniel ML 
Lok, Laurence SC 

Bicomponent pore-forming leukocidins are a family of potent toxins secreted by Staphylococcus aureus, which target white blood cells preferentially and consist of an S- and an F-component. The S-component recognizes a receptor on the host cell, enabling high-affinity binding to the cell surface, after which the toxins form a pore that penetrates the cell lipid bilayer. Until now, six different leukocidins have been described, some of which are host and cell specific. Here, we identify and characterise a novel S. aureus leukocidin; LukPQ. LukPQ is encoded on a 45 kb prophage (ΦSaeq1) found in six different clonal lineages, almost exclusively in strains cultured from equids. We show that LukPQ is a potent and specific killer of equine neutrophils and identify equine-CXCRA and CXCR2 as its target receptors. Although the S-component (LukP) is highly similar to the S-component of LukED, the species specificity of LukPQ and LukED differs. By forming non-canonical toxin pairs, we identify that the F-component contributes to the observed host tropism of LukPQ, thereby challenging the current paradigm that leukocidin specificity is driven solely by the S-component.

Animals, Bacterial Toxins, Cattle, Cell Survival, Gene Order, Horse Diseases, Horses, Host Specificity, Humans, Leukocidins, Neutrophils, Phylogeny, Protein Binding, Receptors, Interleukin-8B, Staphylococcal Infections, Staphylococcus aureus
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Springer Science and Business Media LLC
Medical Research Council (G1001787)
Medical Research Council (MR/P007201/1)
Wellcome Trust (098600/Z/12/Z)
Medical Research Council (MR/N002660/1)
National Institute for Health and Care Research (HICF-T5-342)