C5a peptidase of Streptococcus pyogenes (ScpA)

Molecular Classification

Enzyme, Protease, Cell surface-associated endopeptidase, Adhesin, Invasin

Other Names

Streptococcal C5a peptidase, ScpA, SCPA, C5a-inactivating enzyme

Disease Roles

Infection (specifically, pathogenesis and immune evasion in Streptococcus pyogenes group A streptococcal infections)Other (virulence in invasive and non-invasive streptococcal disease; can influence dissemination and severity in human infections)

C5a peptidase of Streptococcus pyogenes Overview

C5a peptidase (ScpA) of Streptococcus pyogenes is a highly specific, cell-surface endopeptidase and virulence factor that cleaves the His-Lys bond in the complement component C5a, thereby inactivating its chemotactic and pro-inflammatory functions and blunting neutrophil recruitment to sites of infection. ScpA is also capable of cleaving C3 and C3a, expanding its role in disarming complement-driven host defense. Structurally, ScpA is a multidomain enzyme with a signal peptide, an N-terminal subtilisin-like protease domain, fibronectin type III domains, and cell wall anchoring features; it is expressed on the bacterial surface and functions both enzymatically and as an adhesin/invasin for host interactions. Antibodies targeting ScpA can neutralize its function and have shown protection in animal models, making ScpA a promising candidate for vaccine development against group A streptococcal diseases.

Mechanism of Action

Proteolysis of C5a (and C3, C3a) to reduce neutrophil chemotaxis and impair host immune response (Targeting the enzyme, e.g., by vaccination, elicits neutralizing antibodies that block this function, restoring immune recruitment to the site of infection)

Biological Functions

Immune evasion

Proteolytic inactivation of complement factor C5a

Proteolytic inactivation of complement factors C3 and C3a

Adhesion to host cells (epithelial, endothelial)

Invasion of host tissue

Disease Associations

Infection (specifically, pathogenesis and immune evasion in Streptococcus pyogenes group A streptococcal infections)

Other (virulence in invasive and non-invasive streptococcal disease; can influence dissemination and severity in human infections)

Safety Considerations

Potential for autoimmunity or overactivation of the immune response if targeted therapeutically, as C5a peptidase modulates powerful inflammatory mediators of the complement pathway
Cross-reactivity concerns in vaccine design, though studies to date report high immunogenicity and protective responses in animal models without notable safety issues

Interacting Drugs

None approved or in clinical use currently. Some investigational vaccines and inhibitory antibodies have targeted C5a peptidase for preclinical vaccine strategies, but there are no approved pharmacologic inhibitors in clinical practice

Associated Biomarkers

Biomarker
Antibodies to ScpA (may reflect prior infection or vaccine response)
ScpA expression level (in bacteria, could correlate with virulence in infection)