Identification of a staphylococcal complement inhibitor with broad host specificity in equid Staphylococcus aureus strains

J Biol Chem. 2018 Mar 23;293(12):4468-4477. doi: 10.1074/jbc.RA117.000599. Epub 2018 Feb 5.


Staphylococcus aureus is a versatile pathogen capable of causing a broad range of diseases in many different hosts. S. aureus can adapt to its host through modification of its genome (e.g. by acquisition and exchange of mobile genetic elements that encode host-specific virulence factors). Recently, the prophage φSaeq1 was discovered in S. aureus strains from six different clonal lineages almost exclusively isolated from equids. Within this phage, we discovered a novel variant of staphylococcal complement inhibitor (SCIN), a secreted protein that interferes with activation of the human complement system, an important line of host defense. We here show that this equine variant of SCIN, eqSCIN, is a potent blocker of equine complement system activation and subsequent phagocytosis of bacteria by phagocytes. Mechanistic studies indicate that eqSCIN blocks equine complement activation by specific inhibition of the C3 convertase enzyme (C3bBb). Whereas SCIN-A from human S. aureus isolates exclusively inhibits human complement, eqSCIN represents the first animal-adapted SCIN variant that functions in a broader range of hosts (horses, humans, and pigs). Binding analyses suggest that the human-specific activity of SCIN-A is related to amino acid differences on both sides of the SCIN-C3b interface. These data suggest that modification of this phage-encoded complement inhibitor plays a role in the host adaptation of S. aureus and are important to understand how this pathogen transfers between different hosts.

Keywords: SCIN; Staphylococcus aureus (S. aureus); complement system; equine; host adaptation; host-pathogen interaction; immune evasion; innate immunity; microbial pathogenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Complement C3-C5 Convertases / metabolism*
  • Complement C3b / antagonists & inhibitors*
  • Complement C3b / metabolism
  • Complement Inactivator Proteins / chemistry
  • Complement Inactivator Proteins / metabolism*
  • Hemolysis
  • Horses
  • Host Specificity
  • Humans
  • Phagocytosis
  • Protein Binding
  • Staphylococcal Infections / metabolism
  • Staphylococcal Infections / microbiology*
  • Staphylococcus aureus / isolation & purification
  • Staphylococcus aureus / metabolism*
  • Swine
  • Virulence Factors / chemistry
  • Virulence Factors / metabolism*


  • Complement Inactivator Proteins
  • Virulence Factors
  • Complement C3b
  • Complement C3-C5 Convertases

Associated data

  • PDB/3L3O