Multi-functional mechanisms of immune evasion by the streptococcal complement inhibitor C5a peptidase

• DOI: 10.1371/journal.ppat.1006493
• Publication Date: 2017-08-14T17:24:20Z
• Authors: Nicola N. Lynskey; Mark Reglinski; Damien Calay; Matthew K. Siggins; Justin C. Mason; Marina Botto; Shiranee Sriskandan
• Keywords: C3-convertase; Antibody opsonization; Complement control protein; Pathogenesis; Complement component 5

The complement cascade is crucial for clearance and control of invading pathogens, as such a key target pathogen mediated host modulation. C3 the central molecule cascade, plays vital role in opsonization bacteria recruitment neutrophils to site infection. Streptococcal species have evolved multiple mechanisms disrupt complement-mediated innate immunity, among which ScpA (C5a peptidase), C5a inactivating enzyme, widely conserved. Here we demonstrate first time that pyogenic streptococcal are capable cleaving C3, identify C3a novel substrates ScpA, functionally inactivated result cleavage 7 amino acids upstream natural convertase. Cleavage by resulted disruption human neutrophil activation, phagocytosis chemotaxis, while generated abnormally-sized C3b moieties with impaired function, particular reducing deposition on bacterial surface. Despite clear effects complement, expression reduced group A streptococci vivo wildtype C5 deficient mice, promoted systemic dissemination mice lacked both C5, suggesting an additional complement-independent pathogenesis. was shown mediate adhesion epithelial endothelial cells, consistent promoting invasion within host. Taken together, these data show multi-functional virulence factor complement-dependent independent roles