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Prominent Binding of Human and Equine Fibrinogen to Streptococcus equi subsp. zooepidemicus Is Mediated by Specific SzM Types and Is a Distinct Phenotype of Zoonotic Isolates

Bergmann, René ; Jentsch, Maria Christin ; Uhlig, Albrecht ; Müller, Uwe ; van der Linden, Mark ; Rasmussen, Magnus LU ; Waller, Andrew ; von Köckritz-Blickwede, Maren and Baums, Christoph Georg (2020) In Infection and Immunity 88(1).
Abstract

Streptococcus equi subsp. zooepidemicus is an important pathogen in horses that causes severe diseases such as pneumonia and abortion. Furthermore, it is a zoonotic agent, and contact with horses is a known risk factor. In this study, we investigated the working hypothesis that the zoonotic potential varies among S. equi subsp. zooepidemicus strains in association with differences in M-like protein-mediated binding of host plasma proteins. We demonstrate via in-frame deletion mutagenesis of two different S. equi subsp. zooepidemicus strains that the M-like protein SzM is crucial for the binding of fibrinogen to the bacterial surface and for survival in equine and human blood. S. equi subsp. zooepidemicus isolates of equine and human... (More)

Streptococcus equi subsp. zooepidemicus is an important pathogen in horses that causes severe diseases such as pneumonia and abortion. Furthermore, it is a zoonotic agent, and contact with horses is a known risk factor. In this study, we investigated the working hypothesis that the zoonotic potential varies among S. equi subsp. zooepidemicus strains in association with differences in M-like protein-mediated binding of host plasma proteins. We demonstrate via in-frame deletion mutagenesis of two different S. equi subsp. zooepidemicus strains that the M-like protein SzM is crucial for the binding of fibrinogen to the bacterial surface and for survival in equine and human blood. S. equi subsp. zooepidemicus isolates of equine and human origins were compared with regard to SzM sequences and binding of equine and human fibrinogens. The N-terminal 216 amino acids of the mature SzM were found to exhibit a high degree of diversity, but the majority of human isolates grouped in three distinct SzM clusters. Plasma protein absorption assays and flow cytometry analysis revealed that pronounced binding of human fibrinogen is a common phenotype of human S. equi subsp. zooepidemicus isolates but much less so in equine S. equi subsp. zooepidemicus isolates. Furthermore, binding of human fibrinogen is associated with specific SzM types. These results suggest that SzM-mediated binding of human fibrinogen is an important virulence mechanism of zoonotic S. equi subsp. zooepidemicus isolates.

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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
fibrinogen binding, M-like proteins, survival in blood, szm deletion mutant, whole-blood bactericidal assay, zoonosis
in
Infection and Immunity
volume
88
issue
1
article number
e00559-19
publisher
American Society for Microbiology
external identifiers
  • scopus:85076876515
  • pmid:31636136
ISSN
1098-5522
DOI
10.1128/IAI.00559-19
language
English
LU publication?
yes
id
65a2e463-b04b-4282-9940-c4c9c735dd9d
date added to LUP
2020-01-03 12:40:31
date last changed
2024-06-27 11:23:42
@article{65a2e463-b04b-4282-9940-c4c9c735dd9d,
  abstract     = {{<p>Streptococcus equi subsp. zooepidemicus is an important pathogen in horses that causes severe diseases such as pneumonia and abortion. Furthermore, it is a zoonotic agent, and contact with horses is a known risk factor. In this study, we investigated the working hypothesis that the zoonotic potential varies among S. equi subsp. zooepidemicus strains in association with differences in M-like protein-mediated binding of host plasma proteins. We demonstrate via in-frame deletion mutagenesis of two different S. equi subsp. zooepidemicus strains that the M-like protein SzM is crucial for the binding of fibrinogen to the bacterial surface and for survival in equine and human blood. S. equi subsp. zooepidemicus isolates of equine and human origins were compared with regard to SzM sequences and binding of equine and human fibrinogens. The N-terminal 216 amino acids of the mature SzM were found to exhibit a high degree of diversity, but the majority of human isolates grouped in three distinct SzM clusters. Plasma protein absorption assays and flow cytometry analysis revealed that pronounced binding of human fibrinogen is a common phenotype of human S. equi subsp. zooepidemicus isolates but much less so in equine S. equi subsp. zooepidemicus isolates. Furthermore, binding of human fibrinogen is associated with specific SzM types. These results suggest that SzM-mediated binding of human fibrinogen is an important virulence mechanism of zoonotic S. equi subsp. zooepidemicus isolates.</p>}},
  author       = {{Bergmann, René and Jentsch, Maria Christin and Uhlig, Albrecht and Müller, Uwe and van der Linden, Mark and Rasmussen, Magnus and Waller, Andrew and von Köckritz-Blickwede, Maren and Baums, Christoph Georg}},
  issn         = {{1098-5522}},
  keywords     = {{fibrinogen binding; M-like proteins; survival in blood; szm deletion mutant; whole-blood bactericidal assay; zoonosis}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{American Society for Microbiology}},
  series       = {{Infection and Immunity}},
  title        = {{Prominent Binding of Human and Equine Fibrinogen to Streptococcus equi subsp. zooepidemicus Is Mediated by Specific SzM Types and Is a Distinct Phenotype of Zoonotic Isolates}},
  url          = {{http://dx.doi.org/10.1128/IAI.00559-19}},
  doi          = {{10.1128/IAI.00559-19}},
  volume       = {{88}},
  year         = {{2020}},
}