Abstract
Group A Streptococcus (GAS, Streptococcus pyogenes) is an exclusively human pathogen that causes a range of diseases, including pharyngitis, tonsillitis, impetigo, erysipelas, necrotizing fasciitis, and toxic shock syndrome. Post-streptococcal sequelae include acute rheumatic fever and rheumatic heart disease. The bacterium produces a large arsenal of virulence factors that contribute to host tissue adhesion/colonization, bacterial spread, and host immune evasion. Immune evasion factors include proteins that interfere with complement, a system of plasma proteins that are activated by pathogens resulting in a variety of reactions on the surface of the pathogen. This leads to the activation of active components with a variety of effector functions, such as cell lysis, opsonization, and chemotaxis of phagocytes to the site of infection. We have recently identified a novel “complement evasion factor” (CEF) in S. pyogenes. CEF directly interacts with complement proteins C1r, C1s, C3, and C5, interrupts all three complement pathways, and prevents opsonization of the bacterial surface with C3b. We here present methods used to analyze the complement interference of CEF.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Botteaux A, Budnik I, Smeesters PR (2018) Group A streptococcus infections in children: from virulence to clinical management. Curr Opin Infect Dis 31(3):224–230. https://doi.org/10.1097/QCO.0000000000000452
Cunningham MW (2000) Pathogenesis of group A streptococcal infections. Clin Microbiol Rev 13(3):470–511
Stevens DL, Bryant AE (2016) Severe group A streptococcal infections. In: Ferretti JJ, Stevens DL, Fischetti VA (eds) Streptococcus pyogenes : basic biology to clinical manifestations. University of Oklahoma Health Sciences Center (c) The University of Oklahoma Health Sciences Center, Oklahoma City. (OK)
Hurst JR, Brouwer S, Walker MJ, McCormick JK (2021) Streptococcal superantigens and the return of scarlet fever. PLoS Pathog 17(12):e1010097. https://doi.org/10.1371/journal.ppat.1010097
Wessels MR (2016) Pharyngitis and scarlet Ffever. In: Ferretti JJ, Stevens DL, Fischetti VA (eds) Streptococcus pyogenes : basic biology to clinical manifestations. Oklahoma City (OK)
Cunningham MW (2012) Streptococcus and rheumatic fever. Curr Opin Rheumatol 24(4):408–416. https://doi.org/10.1097/BOR.0b013e32835461d3
Martin WJ, Steer AC, Smeesters PR, Keeble J, Inouye M, Carapetis J, Wicks IP (2015) Post-infectious group A streptococcal autoimmune syndromes and the heart. Autoimmun Rev 14(8):710–725. https://doi.org/10.1016/j.autrev.2015.04.005
Barnett TC, Cole JN, Rivera-Hernandez T, Henningham A, Paton JC, Nizet V, Walker MJ (2015) Streptococcal toxins: role in pathogenesis and disease. Cell Microbiol 17(12):1721–1741. https://doi.org/10.1111/cmi.12531
Brouwer S, Barnett TC, Rivera-Hernandez T, Rohde M, Walker MJ (2016) Streptococcus pyogenes adhesion and colonization. FEBS Lett 590(21):3739–3757. https://doi.org/10.1002/1873-3468.12254
Nakata M, Kreikemeyer B (2021) Genetics, structure, and function of group A streptococcal pili. Front Microbiol 12:616508. https://doi.org/10.3389/fmicb.2021.616508
Proft T, Fraser JD (2007) Streptococcal superantigens. Chem Immunol Allergy 93:1–23. https://doi.org/10.1159/000100851
Reglinski M, Sriskandan S (2014) The contribution of group A streptococcal virulence determinants to the pathogenesis of sepsis. Virulence 5(1):127–136. https://doi.org/10.4161/viru.26400
Wilde S, Johnson AF, LaRock CN (2021) Playing with fire: proinflammatory virulence mechanisms of group A streptococcus. Front Cell Infect Microbiol 11:704099. https://doi.org/10.3389/fcimb.2021.704099
Laabei M, Ermert D (2019) Catch Me if You Can: Streptococcus pyogenes complement evasion strategies. J Innate Immun 11(1):3–12. https://doi.org/10.1159/000492944
Okumura CY, Nizet V (2014) Subterfuge and sabotage: evasion of host innate defenses by invasive Gram-positive bacterial pathogens. Annu Rev Microbiol 68:439–458. https://doi.org/10.1146/annurev-micro-092412-155711
Syed S, Viazmina L, Mager R, Meri S, Haapasalo K (2020) Streptococci and the complement system: interplay during infection, inflammation and autoimmunity. FEBS Lett 594(16):2570–2585. https://doi.org/10.1002/1873-3468.13872
Nesargikar PN, Spiller B, Chavez R (2012) The complement system: history, pathways, cascade and inhibitors. Eur J Microbiol Immunol (Bp) 2(2):103–111. https://doi.org/10.1556/EuJMI.2.2012.2.2
Riihila P, Nissinen L, Knuutila J, Rahmati Nezhad P, Viiklepp K, Kahari VM (2019) Complement system in cutaneous squamous cell carcinoma. Int J Mol Sci 20(14). https://doi.org/10.3390/ijms20143550
Lynskey NN, Reglinski M, Calay D, Siggins MK, Mason JC, Botto M, Sriskandan S (2017) Multi-functional mechanisms of immune evasion by the streptococcal complement inhibitor C5a peptidase. PLoS Pathog 13(8):e1006493. https://doi.org/10.1371/journal.ppat.1006493
Fernie-King BA, Seilly DJ, Willers C, Wurzner R, Davies A, Lachmann PJ (2001) Streptococcal inhibitor of complement (SIC) inhibits the membrane attack complex by preventing uptake of C567 onto cell membranes. Immunology 103(3):390–398. https://doi.org/10.1046/j.1365-2567.2001.01249.x
von Pawel-Rammingen U (2012) Streptococcal IdeS and its impact on immune response and inflammation. J Innate Immun 4(2):132–140. https://doi.org/10.1159/000332940
Collin M, Olsen A (2001) EndoS, a novel secreted protein from Streptococcus pyogenes with endoglycosidase activity on human IgG. EMBO J 20(12):3046–3055. https://doi.org/10.1093/emboj/20.12.3046
Honda-Ogawa M, Sumitomo T, Mori Y, Hamd DT, Ogawa T, Yamaguchi M, Nakata M, Kawabata S (2017) Streptococcus pyogenes endopeptidase O contributes to evasion from complement-mediated bacteriolysis via binding to human complement factor C1q. J Biol Chem 292(10):4244–4254. https://doi.org/10.1074/jbc.M116.749275
Lambris JD, Ricklin D, Geisbrecht BV (2008) Complement evasion by human pathogens. Nat Rev Microbiol 6(2):132–142. https://doi.org/10.1038/nrmicro1824
Zipfel PF, Skerka C (2014) Staphylococcus aureus: the multi headed hydra resists and controls human complement response in multiple ways. Int J Med Microbiol 304(2):188–194. https://doi.org/10.1016/j.ijmm.2013.11.004
Aghababa H, Ting YT, Pilapitiya D, Loh JMS, Young PG, Proft T (2022) Complement evasion factor (CEF), a novel immune evasion factor of Streptococcus pyogenes. Virulence 13(1):225–240. https://doi.org/10.1080/21505594.2022.2027629
Lorenz N, Clow F, Radcliff FJ, Fraser JD (2013) Full functional activity of SSL7 requires binding of both complement C5 and IgA. Immunol Cell Biol 91(7):469–476. https://doi.org/10.1038/icb.2013.28
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2023 The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature
About this protocol
Cite this protocol
Aghababa, H., Loh, J.M.S., Proft, T. (2023). Methods to Analyze the Contribution of Complement Evasion Factor (CEF) to Streptococcus pyogenes Virulence. In: Nordenfelt, P., Collin, M. (eds) Bacterial Pathogenesis. Methods in Molecular Biology, vol 2674. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-3243-7_8
Download citation
DOI: https://doi.org/10.1007/978-1-0716-3243-7_8
Published:
Publisher Name: Humana, New York, NY
Print ISBN: 978-1-0716-3242-0
Online ISBN: 978-1-0716-3243-7
eBook Packages: Springer Protocols