Department of Farm Animal Health, Faculty of Veterinary Medicine, Utrecht University, 3584 CL, Utrecht, The Netherlands.
Medical Microbiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
Sci Rep. 2017 Jan 20;7:40660. doi: 10.1038/srep40660.
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.
双成分孔形成白细胞毒素是金黄色葡萄球菌分泌的一类强效毒素，它们优先靶向白细胞，由 S 成分和 F 成分组成。S 成分识别宿主细胞上的受体，使其能够与细胞表面高亲和力结合，然后毒素形成一个穿透细胞脂双层的孔。到目前为止，已经描述了六种不同的白细胞毒素，其中一些具有宿主和细胞特异性。在这里，我们鉴定并表征了一种新型的金黄色葡萄球菌白细胞毒素 LukPQ。LukPQ 编码在一个 45kb 的噬菌体（ΦSaeq1）上，该噬菌体存在于六个不同的克隆谱系中，几乎只存在于从马类动物培养的菌株中。我们表明 LukPQ 是一种强效且特异性的马属动物中性粒细胞杀伤剂，并鉴定出马属动物-CXCRA 和 CXCR2 是其靶受体。尽管 S 成分（LukP）与 LukED 的 S 成分高度相似，但 LukPQ 和 LukED 的物种特异性不同。通过形成非典型的毒素对，我们发现 F 成分有助于 LukPQ 观察到的宿主趋向性，从而挑战了白细胞毒素特异性仅由 S 成分驱动的当前范式。
