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

作者：Gerrit Koop, Manouk Vrieling, Daniel M. L. Storisteanu, Laurence S. C. Lok, Tom P. Monie, Glenn F. van Wigcheren, Claire L. Raisen, Xiaoliang Ba, Nicholas Gleadall, Nazreen F. Hadjirin, Arjen J. Timmerman, Jaap A. Wagenaar, H. Klunder, J. Ross Fitzgerald, Ruth N. Zadoks, Gavin K. Paterson, Cármen Torres, Andrew Stephen Waller, Anette Loeffler, Igor Loncaric, Armando E. Hoet, Karin Bergström, Luisa De Martino, Constança Pomba, Herminia de LENCASTRE, Karim Ben Slama, Haythem Gharsa, Emily J. Richardson, Edwin R. Chilvers, Carla J. C. de Haas, Kok van Kessel, Jos A. G. van Strijp, Ewan M. Harrison, Mark A. Holmes · 发表于：Scientific Reports · 年份：2017 · DOI：10.1038/srep40660 · 被引用次数：71 · 研究领域：Antimicrobial Resistance in Staphylococcus、Streptococcal Infections and Treatments、Bacterial Genetics and Biotechnology

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.