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

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

Author information

1
From the Department of Medical Microbiology, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, The Netherlands.
2
the Roslin Institute, University of Edinburgh, Easter Bush Campus, Midlothian EH25 9RG, United Kingdom.
3
the Department of Biochemistry and Molecular Biophysics, Kansas State University, Manhattan, Kansas 66506.
4
the Department of Farm Animal Health, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht, The Netherlands.
5
the Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, United Kingdom, and.
6
the Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom.
7
From the Department of Medical Microbiology, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, The Netherlands, s.h.m.rooijakkers@umcutrecht.nl.

Abstract

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

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