Streptococcus suis DNase SsnA contributes to degradation of neutrophil extracellular traps (NETs) and evasion of NET-mediated antimicrobial activity.
Streptococcus suis is an important cause of different pathologies in pigs and humans, most importantly fibrinosuppurative meningitis. Tissue infected with this pathogen is substantially infiltrated with neutrophils, but the function of neutrophil extracellular traps (NETs) - a more recently discovered antimicrobial strategy of neutrophils - in host defence against Strep. suis has not been investigated. The objective of this work was to investigate the interaction of Strep. suis with NETs in vitro. Strep. suis induced NET formation in porcine neutrophils and was entrapped but not killed by those NETs. As the amount of NETs decreased over time, we hypothesized that a known extracellular DNase of Strep. suis degrades NETs. Though this nuclease was originally designated Strep. suis-secreted nuclease A (SsnA), this work demonstrated surface association in accordance with an LPXTG cell wall anchor motif and partial release into the supernatant. Confirming our hypothesis, an isogenic ssnA mutant was significantly attenuated in NET degradation and in protection against the antimicrobial activity of NETs as determined in assays with phorbol myristate acetate (PMA)-stimulated human neutrophils. Though assays with PMA-stimulated porcine neutrophils suggested that SsnA also degrades porcine NETs, phenotypic differences between wt and the isogenic ssnA mutant were less distinct. As SsnA expression was crucial for neither growth in vitro nor for survival in porcine or human blood, the results indicated that SsnA is the first specific NET evasion factor to be identified in Strep. suis.
Institute for Microbiology, Centre for Infection Medicine, University of Veterinary Medicine Hannover, Hannover, Germany.
Nicole
N
de Buhr
Department of Physiological Chemistry, Centre for Infection Medicine, University of Veterinary Medicine Hannover, Hannover, Germany.
Ariane
A
Neumann
Department of Physiological Chemistry, Centre for Infection Medicine, University of Veterinary Medicine Hannover, Hannover, Germany.
Natalja
N
Jerjomiceva
Department of Physiological Chemistry, Centre for Infection Medicine, University of Veterinary Medicine Hannover, Hannover, Germany.
Maren
M
von Köckritz-Blickwede
Institute for Microbiology, Centre for Infection Medicine, University of Veterinary Medicine Hannover, Hannover, Germany.
Christoph G
CG
Baums
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001704:Biopolymers / Q000378:metabolism*; D002478:Cells, Cultured; D003851:Deoxyribonucleases / Q000235:genetics / Q000378:metabolism*; D055786:Gene Knockout Techniques; D054884:Host-Pathogen Interactions; D006801:Humans; D006868:Hydrolysis; D009504:Neutrophils / Q000276:immunology*; D017011:Streptococcus suis / Q000201:enzymology* / Q000276:immunology*; D013552:Swine
D001426:Bacterial Proteins; D001704:Biopolymers; D003851:Deoxyribonucleases