Identification of a staphylococcal complement inhibitor with broad host specificity in equid Staphylococcus aureus strains
De Jong, Nienke W.M.; Vrieling, Manouk; Garcia, Brandon L.; Koop, Gerrit; Brettmann, Matt; Aerts, Piet C.; Ruyken, Maartje; Van Strijp, Jos A.G.; Holmes, Mark; Harrison, Ewan M.; Geisbrecht, Brian V.; Rooijakkers, Suzan H.M.
(2018) Journal of Biological Chemistry, volume 293, issue 12, pp. 4468 - 4477
(Article)
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
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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 phageencoded complement inhibitor plays a role in the host adaptation of S. aureus and are important to understand how this pathogen transfers between different hosts.
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Keywords: complement system, innate immunity, Staphylococcus aureus (S. aureus), host-pathogen interaction, microbial pathogenesis, equine, host adaptation, immune evasion, SCIN, Biochemistry, Molecular Biology, Cell Biology
ISSN: 0021-9258
Publisher: American Society for Biochemistry and Molecular Biology Inc.
Note: Funding Information: This work was supported by National Institutes of Health Grants AI113552 and GM121511 (to B. V. G.) and by ERC Starting Grant 639209 (to S. H. M. R.), and this publication presents independent research supported by the Health Innovation Challenge Fund (WT098600, HICF-T5-342), a par-allel funding partnership between the Department of Health and Well-come Trust. The authors declare that they have no conflicts of interest with the contents of this article. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Funding Information: This work was supported by National Institutes of Health Grants AI113552 and GM121511 (to B. V. G.) and by ERC Starting Grant 639209 (to S. H. M. R.), and this publication presents independent research supported by the Health Innovation Challenge Fund (WT098600, HICF-T5-342), a parallel funding partnership between the Department of Health and Wellcome Trust. Publisher Copyright: © 2018 by The American Society for Biochemistry and Molecular Biology, Inc. Published in the U.S.A.
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