Group A Streptococcus C5a peptidase (ScpA)

Group A Streptococcus C5a peptidase (ScpA) is a surface-anchored serine protease produced by Streptococcus pyogenes, a major human pathogen (UniProt P58099; Wikipedia). Its primary biological function is to cleave and inactivate the human complement component C5a, a potent chemoattractant for neutrophils and other phagocytes (PubMed 3906656, 5219). By destroying this signal, ScpA allows the bacteria to evade the host's innate immune response and colonize mucosal surfaces more effectively (Infect. Immun. 1996, 64:503-510). Beyond C5a, ScpA has also been shown to cleave other pro-inflammatory cytokines such as interferon-gamma (IFN-γ) and interleukin-37 (IL-37) (Cytokine 2024, 180:156652). Due to its highly conserved nature across different streptococcal strains and its critical role in virulence, ScpA is a leading candidate for the development of vaccines, such as VAX-A1 and Combo#5 (Vaccine 2004, 22:4332-41; Vaxcyte). Interestingly, recent research has also explored the use of ScpA as a therapeutic enzyme to treat inflammatory conditions like psoriasis by leveraging its ability to degrade overactive cytokines (Int. J. Pharm. 2025, 671:125244).

Other names

SCPAStreptococcal C5a peptidaseC5a inactivatorC5a-inhibitory proteinScpA1

Cleaves the human complement factor C5a at the His67-Lys68 bond, inactivating its chemotactic activity and preventing the recruitment of neutrophils to the site of infection.