Table 1.
Predominant GAS virulence factors, their known mechanisms and targets, and their essentiality in models of invasive (intradermal, subcutaneous, or intravenous) or nasopharyngeal (intranasal) infection.
| Name | Function | Target(s) | In vivo requirement? | |
|---|---|---|---|---|
| Invasive | Intranasal | |||
| Streptococcal pyrogenic exotoxin (Spe A, C, G, H, I, J, K, L, M, Q, R); SmeZ; SSA | Superantigen (binding activity) |
TCR, MHC, potentially co-receptors | N (Walker et al., 2014) | Y (Turner et al., 2012; Kasper et al., 2014) |
| Streptococcal pyrogenic exotoxin B (SpeB) | Protease | IL-1β, 100+ other host & GAS proteins | N (LaRock et al., 2016) | Y (LaRock et al., 2020) |
| ScpA | Protease | C5a | N (Walker et al., 2014) | Y (Ji et al., 1997) |
| Streptokinase (Ska) | Protease | Plasminogen activator | Y (Sun et al., 2004) | ? |
| SpyCEP/ScpC | Protease | IL-8 | Y (Zinkernagel et al., 2008) | ? |
| IdeS/Mac | Mimicry, Protease | FcγRIIIB; IgG opsonophagocytis |
N (Okumura et al., 2013) | ? |
| Sda1 | DNase | NETs | Y (Walker et al., 2007) | Y (Tanaka et al., 2020) |
| Nga | Glycohydrolase | NAD+, unknown other | N (Cole et al., 2010) | ? |
| Streptococcal 5′-nucleotidase A (S5nA) | Hydrolase | Nucleosides (AMP, ADP, ATP) | Y (Soh et al., 2020) | ? |
| Streptolysin O (SLO) | Pore-forming toxin | Epithelial & leukocyte membranes | N (Steer et al., 2009) Y (Timmer et al., 2009) | ? |
| Streptolysin S (SLS) | Pore-forming toxin | Erythrocyte membranes | N (Hall et al., 2004) Y (Betschel et al., 1998) | ? |
| M protein | Adhesion, Sequestration | LL-37, histones, albumin, plasminogen, fibrinogen, CD46, Ig, C3b, factor H, C4b-BP | N (Cole et al., 2010) Y (Ashbaugh et al., 1998) | Y (Anderson et al., 2014) |
| T antigen | Adherence | Fibronectin, collagen | Y (Chen et al., 2020) | ? |
| Protein S | Sequestration | Erythrocyte fragments | Y (Wierzbicki et al., 2019) | ? |
| SIC | Sequestration | Lysozyme, kininogen, defensins, LL-37, C5b | Y (Frick et al., 2003) | Y (Lukomski et al., 2000) |
| EndoS | Endo-β-N-acetylglucosaminidase | IgG | N (Sjögren et al., 2011) | ? |
| SpyA | ADP ribosyltransferase | Actin, vimentin, others? | Y (Hoff et al., 2011) | ? |
| SodA | Superoxide dismutase | Reactive oxygen species | Y (Ricci et al., 2002; Janulczyk et al., 2003) | ? |
| HasABC | Hyaluronic acid capsule | Antimicrobials, CD44 | N (Henningham et al., 2014) | Y (Cywes et al., 2000) |
TCR, T cell receptor; MHC, Major histocompatibility complex; NET; neutrophilic extracellular trap; IL, interleukin; FcγRIIIB, Fcγ receptor type III, also referred to as CD16.