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Streptococcus suis DNase SsnA contributes to degradation of neutrophil extracellular traps (NETs) and evasion of NET-mediated antimicrobial activity

de Buhr, Nicole; Neumann, Ariane LU ; Jerjomiceva, Natalja; von Köckritz-Blickwede, Maren and Baums, Christoph G (2014) In Microbiology 160. p.95-385
Abstract

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... (More)

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.

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publication status
published
keywords
Animals, Bacterial Proteins, Biopolymers, Cells, Cultured, Deoxyribonucleases, Gene Knockout Techniques, Host-Pathogen Interactions, Humans, Hydrolysis, Neutrophils, Streptococcus suis, Swine, Journal Article, Research Support, Non-U.S. Gov't
in
Microbiology
volume
160
pages
11 pages
publisher
MAIK Nauka/Interperiodica
external identifiers
  • scopus:84893447723
ISSN
1465-2080
DOI
10.1099/mic.0.072199-0
language
English
LU publication?
no
id
bed0aa79-4cd0-46b7-95b2-d5c5df4cb6eb
date added to LUP
2017-09-19 12:21:49
date last changed
2017-09-24 05:15:36
@article{bed0aa79-4cd0-46b7-95b2-d5c5df4cb6eb,
  abstract     = {<p>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.</p>},
  author       = {de Buhr, Nicole and Neumann, Ariane and Jerjomiceva, Natalja and von Köckritz-Blickwede, Maren and Baums, Christoph G},
  issn         = {1465-2080},
  keyword      = {Animals,Bacterial Proteins,Biopolymers,Cells, Cultured,Deoxyribonucleases,Gene Knockout Techniques,Host-Pathogen Interactions,Humans,Hydrolysis,Neutrophils,Streptococcus suis,Swine,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  pages        = {95--385},
  publisher    = {MAIK Nauka/Interperiodica},
  series       = {Microbiology},
  title        = {Streptococcus suis DNase SsnA contributes to degradation of neutrophil extracellular traps (NETs) and evasion of NET-mediated antimicrobial activity},
  url          = {http://dx.doi.org/10.1099/mic.0.072199-0},
  volume       = {160},
  year         = {2014},
}