Table 1.
Pathogen-derived nucleases that degrade ETs.
| Pathogene | Nuclease | Nuclease activity | Cellular localization | ET degradation* | Conserved motifs | Reference |
|---|---|---|---|---|---|---|
| Vibrio cholerae | Xds | Exonuclease | Membrane anchored | Deletion mutant increased PMA-inducted NETs in human neutrophils. | LTD, OBD, EEPD | (11–13) |
| Dns | Endonuclease | Extracellular secreted | Deletion mutant increased PMA-inducted NETs in human neutrophils. | ND | (11, 12) | |
| Streptococcus pneumoniae | EndA | Endonuclease | Membrane anchored | Deletion mutant failed to degrade NETs induced by PMA or H2O2 in human neutrophils In vivo: NETs localized to alveoli in deletion mutant-infected lungs of C57BL/6 mice. |
DRGH, HNH(N) | (14–20) |
| TatD | Exo/endonuclease | Cell-wall surface anchored | rTatD expressed in E. coli degraded PMA-inducted NETs in human neutrophils, but little degrading activity in deletion mutant. | ND | (21) | |
| Group A Streptococcus | Sda1 | DNase | Cell-wall anchored | Significant quantities of NETs persisted in human neutrophils infected with deletion mutant; Sda1-expressing L. lactis eliminated NETs in human neutrophils. In vivo: NETs were clearly visualized in murine skin abscess model injected with deletion mutant. |
LPXTG, DRSH | (22) |
| Streptococcus pyogenes | SpnA | Exo/endonuclease | Cell-wall anchored | Deletion mutant increased PMA-inducted NETs in human neutrophils; rSpnA expressed in E. coli and SpnA-expressing L. lactis cleaved PMA-inducted NETs in human neutrophils. | LPXTG, EEPD, OBD | (23, 24) |
| Streptococcus suis | SsnA | DNase | Cell-wall anchored | Deletion mutant attenuated NET degradation in PMA-stimulated human neutrophils, but not porcine. | LPXTG | (25) |
| EndAsuis | Endonuclease | Membrane anchored | Deletion mutant attenuated NET degradation in PMA-stimulated human neutrophils during exponential growth, but not in stationary phase. | DRGH | (26) | |
| Streptococcus equi subsp. zooepidemicus | ENuc | Sugar non-specific nuclease | Cell-wall anchored | rENuc expressed in E. coli degraded PMA-inducted NETs in neutrophils of ICR mice. | LPXTG, sugar-nonspecific nuclease domain, EEPD | (27) |
| 5Nuc | 5’-nucleotidase | Cell-wall anchored | r5Nuc expressed in E. coli degraded PMA-inducted NETs in neutrophils of ICR mice. | LPXTG, 5’-nucleotidase domain | ||
| Streptococcus agalactiae | NucA | Exo/endonuclease | Extracellular secreted | The nucA H148A mutant had no effect on NET response in PMA-activated mice neutrophils. | DKGH, HNN | (28, 29) |
| Streptococcus mutans | DeoC | Nuclease | ND | Deletion mutant stimulated NET production in human neutrophils. | ND | (30) |
| Streptococcus sanguis | SWAN | Sugar non-specific nuclease | Cell-wall anchored | rSWAN expressed in E. coli digested PMA-inducted NETs in human neutrophils | LPKTG, EEPD, OBD | (31) |
| Streptococcus iniae | SpnAi | ND | ND | rSpnAi expressed in E. coli degraded PMA-inducted NETs in neutrophils from adult zebrafish kidney. | ND | (32) |
| Staphylococcus aureus | Nuc1/SNase | Sugar non-specific nuclease | Extracellular secreted | Deletion mutant showed impaired degradation of PMA-inducted NETs in human neutrophils; Snase-expressing L. lactis cleaved PMA-induced NETs in neutrophils of NOD mice. | ND | (33–39) |
| Mycobacterium tuberculosis | Rv0888 | Exo/endonuclease, Phosphatase, Smase | Extracellular secreted/ Membrane anchored |
The Smase activity of Rv0888 efficiently induced NET formation in human neutrophils, but not nuclease activity. | ND | (40–42) |
| Pseudomonas aeruginosa | EddB | DNase, PDE | Extracellular secreted | The EddAB double mutant with plasmid-encoded pEddB restored the NET degradation capacity in human neutrophils. | ND | (43) |
| Neisseria gonorrhoeae | Nuc | Sugar non-specific nuclease | Extracellular secreted | rNuc expressed in E. coli decreased the integrity of PMA-induced NETs in human neutrophils, as well as NETs elicited by the deletion mutant. | ND | (44) |
| Prevotella intermedius | nucA | Sugar non-specific nuclease | Extracellular secreted | rNucA expressed in E. coli was capable of cleaving PMA-induced NETs in human neutrophils. | EEPD | (45) |
| nucD | Sugar non-specific nuclease | Extracellular secreted | rNucD expressed in E. coli was capable of cleaving PMA-induced NETs in human neutrophils. | Endonuclease_NS domain | ||
| Ralstonia solanacearum | NucA/NucB | Endonuclease | Membrane anchored | The nucA/B deletion mutant was immobilized by the DNA of plant border cell traps, and reversed by rNucA and rNucB expressed in E. coli. | ND | (46) |
| Leishmania spp. | 3’NT/NU | Sugar non-specific nuclease | Cell surface membrane-anchored | LP parasites with higher 3’NT/NU activity cleaved more NETs in buffy coat neutrophils. | Class I nucleases domain | (47–49) |
| Nippostrongylus brasiliensis | Nb-DNase | DNase II | ND | The extracellular DNA fibers formed in human neutrophils induced by PMA were hydrolyzed by rNb-DNase II expressed in E. coli. | DNase II | (50) |
| Plasmodium spp. | PbTatD | DNase | Parasitophorous vacuole membrane | The deletion mutant induced METs and NETs in J774A.1 macrophages and mouse neutrophils, but fewer in WT parasites; rPbTatD expressed in E. coli hydrolyzed METs. | DNase | (51, 52) |
| Trypanosoma spp. | TryTatD05/TryTatD15 | Endonuclease | Cytoplasm, flagella |
rTryTatD05 and rTryTatD15 expressed in E. coli degraded NETs in murine neutrophils. | HPEDHRHFGEDP | (53) |
| Mycoplasma hominis | MHO_0730 | Sugar non-specific nuclease | Membrane anchored | Viable Mycoplasma hominis degraded PMA-induced NETs in human neutrophils. | TNASE_3 domain | (54, 55) |
| Mycoplasma hyopneumoniae | Mhp597 | Sugar non-specific nuclease | Extracellular secreted | PMA-induced NETs in porcine were completely destroyed by rMhp597 expressed in E. coli. | ND | (56) |
| Mycoplasma bovis | MBOV_RS02825 | Sugar non-specific nuclease | Membrane anchored | rMBOV_RS02825 expressed in E. coli reduced PMA-induced NETs in bovine neutrophils. | TNASE_3 domain | (57) |
| MnuA | ND | Membrane anchored | NETs were evident in cow neutrophils stimulated with the deletion mutant. | ND | (58) | |
| Mycoplasma pneumoniae | Mpn491 | Nuclease | Extracellular secreted | The ability of the deletion mutant to degrade PMA-induced NETs in human PMNs was markedly impaired. In vivo: LPS-induced NETs in mice lungs were apparently released by the infection with the deletion mutant. |
EEPD | (59) |
| Leptospira spp. | LigA | Exo/endonuclease | Surface Protein | rLigA expressed in E. coli degraded the PMA-induced NETs in neutrophils of C57BL/6J mice. | ND | (60) |
*Conditions under which pathogen-derived nucleases degrade ETs in vitro and in vivo.
ND, not determined; ETs, extracellular traps; NETs, neutrophil extracellular traps; PMA, phorbol myristate acetate; Smase, sphingomyelinase; PDE, phosphodiesterase; LTD, lamin-tail domain; OBD, oligonucleotide/oligosaccharide-binding fold domain; EEPD, endonuclease/exonuclease/phosphatase domain.