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

Sci Rep. 2017 Jan 20;7:40660. doi: 10.1038/srep40660.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Toxins / genetics
  • Bacterial Toxins / metabolism
  • Cattle
  • Cell Survival
  • Gene Order
  • Horse Diseases / microbiology
  • Horses
  • Host Specificity
  • Humans
  • Leukocidins / genetics*
  • Leukocidins / metabolism*
  • Neutrophils / metabolism
  • Phylogeny
  • Protein Binding
  • Receptors, Interleukin-8B / metabolism
  • Staphylococcal Infections / microbiology
  • Staphylococcus aureus / genetics*
  • Staphylococcus aureus / metabolism*

Substances

  • Bacterial Toxins
  • Leukocidins
  • Receptors, Interleukin-8B