Table 1.
Bacterial proteases and their targets in the innate immune system
| Protease name(s) | Catalytic type/clan/family(a) | Targets | Pathogen |
|---|---|---|---|
| Staphopain A (ScpA) | cysteine/CA/C47 | contact activation (HMWK) | Staphylococcus aureus |
| Staphopain B (SspB) | cysteine/CA/C47 | 1 contact activation (HMWK) 2 phagocytes (neutrophils and monocytes) |
S. aureus |
| Aureolysin | metallo/MA/M4 | 1 AMPs (LL-37) 2 cytokine receptors (IL-6R) |
S. aureus |
| Streptopain (SpeB) | cysteine/CA/C10 | 1 contact activation (HMWK) 2 complement (C3, properdin) 3 AMPs (LL-37) 4 phagocytes (neutrophils) 5 cytokines [IL-1β precursor (pIL-1 β)] 6 phagocyte function (uPAR) |
Streptococcus pyogenes (GAS) |
| C5a peptidase (ScpA) | serine/SB/S8 | complement (C5a) | S. pyogenes (GAS) |
| SlyCEP (ScpC) | serine/SB/S8/ | chemokines (IL-8, KC, MIP-2, GCP-2, GROα) | S. pyogenes (GAS) |
| Gingipains [Lys-specific gingipain (Kgp) and Arg-specific gingipains (RgpA and RgpB)] | cysteine/CD/C25 | 1 contact activation (HMWK and prekallikrain) 2 complement 3 AMPs (LL-37, dermaseptin, cecripin B, brevinin, HNP-1, hBD-1, hBD-2) 4 PAR signaling 5 chemokines (IL-8) 6 phagocytes (neutrophils) 7 iron scavenging (hemoglobin degradation) 8 cytokines (IL-1β, IL-6, IL-12, IL-1ra, TNF-α, IFN-γ) 9 cytokine receptors (IL-6R,) 10 10 phagocyte functions (C5aR, CD14) |
Porphyromonas gingivalis |
| Pla (plasminogen activator) | aspartyl/AF/A26 | fibrinolysis (plasminogen, α2-antiplasmin) | Yersinia pestis |
| PgtE (OmpE, protein E) | aspartyl/AF/A26 | 1 complement (C3b, C4b, C5) 2 AMPs (LL-37) |
Salmonella enterica serovar Typhimurium |
| OmpT (opmtin) | aspartyl/AF/A20 | AMPs (protamine) | Escherichia coli |
| StcE | metallo/MA/M66 | complement (C1-inhibitor) | E. coli O157:H7 |
| ElaD | cysteine/CE/C79 | inflammatory signaling pathway (deubiquitination) | E. coli |
| Hbp (Tsh peptidase) | serine/PA/S10 | iron scavenging (Hb) | E. coli |
| Gelatinase (GelE, coccolysin) | metallo/MA/M4 | 1 complement (C3) 2 AMPs (LL-37) |
Enterococcus faecalis |
| YopJ/YopP | cysteine/CE/C55 | inflammatory signaling pathway | Yersinia pseudotuberculosis, Yersinia enterocolitica |
| SseL (ElaD) | cysteine/CE/C79 | inflammatory signaling pathway (deubiquitination) | S. enterica serovar Typhimurium |
| CWyDuM and ChlyDub2 | cysteine/CE/C48 | inflammatory signaling pathway (deubiquitination and de-NEDDylation) | Chlamydia trachomatis |
| XopD | cysteine/CE/C48 | inflammatory signaling pathway (de-SUMOlylation) | Xanthomonas campestris |
| YopT | cysteine/CA/C58 | actin polymerization (small GTPases) | Y. pestis |
| AvrPphB | cysteine/CA/C58 | intracellular signaling (small GTPases) | Pseudomonas syringae |
| Anthrax lethal toxin | metallo/MA/M34 | inflammatory signaling pathway (MKK) | Bacillus anthracis |
| SufA | serine/SB/S8 | AMPs (LL-37) | Finegoldia magna |
| ZapA (mirabilysin) | metallo/MA/M10 | 1 AMPs (LL-37, hBD1) 2 complement (C1q and C3) |
Proteus mirabilis |
| Protease name(s) | Catalytic type/clan/family(a) | Targets | Pathogen |
| Elastase (LasB, pseudolysin) | metallo/MA/M4 | 1 AMPs (LL-37) 2 PAR-2 3 chemokines (RANTES, MCP-1, ENA-78) 4 cytokines (IL-6, IL-8, IFN-γ) 5 cytokine receptors (IL-6R) 6 phagocyte functions (uPAR, fMLP receptor) |
Pseudomonas aeruginosa |
| Alkaline protease (aeruginolysin) | metallo/MA/M10 | chemokines (RANTES, MCP-1, ENA-78) | P. aeruginosa |
| LasA protease (staphylolysin) | metallo/MO/M23 | AMPs (IFN-γ, IL-2) | P. aeruginosa |
| LepA | serine/SB/S8 | PARs | P. aeruginosa |
| Serralysin | metallo/MA/M10 | 1 PAR-2 2 cytokine receptors (IL-6R) |
Serratia marcescens |
| Dentilisin (PrtP, trepolisin) | serine/SB/S8 | 1 cytokines (IL-1 β, IL-6, TNF-α) 2 complement (C3) |
Treponema denticola |
| Msp peptidase | metallo/MA/M4 | cytokines (IL-2) | Legionella pneumophila |
GAS = Group A streptococcus.
1Classification of proteases is based on the evolutionary and structural relationship among enzymes, inferred from the comparison of amino acid sequence and/or tertiary structures. The term family is used to describe a group of proteases in which members show reciprocal evolutionary relationship. Families are clustered into clans. A clan contains all the present proteases that evolved from a single origin. For details see the MEROPS database: http://merops.sanger.ac.uk.