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A rapid method for selecting suitable animal species for studying pathogen interactions with plasma protein ligands in vivo

Naudin, Clément LU ; Schumski, Ariane; Salo-Ahen, Outi M H; Herwald, Heiko LU and Smeds, Emanuel LU (2017) In Microbial Biotechnology 10(3). p.657-665
Abstract

Species tropism constitutes a serious problem for developing relevant animal models of infection. Human pathogens can express virulence factors that show specific selectivity to human proteins, while their affinity for orthologs from other species can vary significantly. Suitable animal species must be used to analyse whether virulence factors are potential targets for drug development. We developed an assay that rapidly predicts applicable animal species for studying virulence factors binding plasma proteins. We used two well-characterized Staphylococcus aureus proteins, SSL7 and Efb, to develop an ELISA-based inhibition assay using plasma from different animal species. The interaction between SSL7 and human C5 and the binding of Efb... (More)

Species tropism constitutes a serious problem for developing relevant animal models of infection. Human pathogens can express virulence factors that show specific selectivity to human proteins, while their affinity for orthologs from other species can vary significantly. Suitable animal species must be used to analyse whether virulence factors are potential targets for drug development. We developed an assay that rapidly predicts applicable animal species for studying virulence factors binding plasma proteins. We used two well-characterized Staphylococcus aureus proteins, SSL7 and Efb, to develop an ELISA-based inhibition assay using plasma from different animal species. The interaction between SSL7 and human C5 and the binding of Efb to human fibrinogen and human C3 was studied. Affinity experiments and Western blot analyses were used to validate the assay. Human, monkey and cat plasma interfered with binding of SSL7 to human C5. Binding of Efb to human fibrinogen was blocked in human, monkey, gerbil and pig plasma, while human, monkey, gerbil, rabbit, cat and guinea pig plasma inhibited the binding of Efb to human C3. These results emphasize the importance of choosing correct animal models, and thus, our approach is a rapid and cost-effective method that can be used to prevent unnecessary animal experiments.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Microbial Biotechnology
volume
10
issue
3
pages
657 - 665
publisher
John Wiley and Sons Ltd
external identifiers
  • scopus:85013004895
  • wos:000400019700015
ISSN
1751-7907
DOI
10.1111/1751-7915.12601
language
English
LU publication?
yes
id
a285da7d-17e4-4edf-92a9-e0e6d17bef61
date added to LUP
2017-03-01 13:30:55
date last changed
2018-01-07 11:53:25
@article{a285da7d-17e4-4edf-92a9-e0e6d17bef61,
  abstract     = {<p>Species tropism constitutes a serious problem for developing relevant animal models of infection. Human pathogens can express virulence factors that show specific selectivity to human proteins, while their affinity for orthologs from other species can vary significantly. Suitable animal species must be used to analyse whether virulence factors are potential targets for drug development. We developed an assay that rapidly predicts applicable animal species for studying virulence factors binding plasma proteins. We used two well-characterized Staphylococcus aureus proteins, SSL7 and Efb, to develop an ELISA-based inhibition assay using plasma from different animal species. The interaction between SSL7 and human C5 and the binding of Efb to human fibrinogen and human C3 was studied. Affinity experiments and Western blot analyses were used to validate the assay. Human, monkey and cat plasma interfered with binding of SSL7 to human C5. Binding of Efb to human fibrinogen was blocked in human, monkey, gerbil and pig plasma, while human, monkey, gerbil, rabbit, cat and guinea pig plasma inhibited the binding of Efb to human C3. These results emphasize the importance of choosing correct animal models, and thus, our approach is a rapid and cost-effective method that can be used to prevent unnecessary animal experiments.</p>},
  author       = {Naudin, Clément and Schumski, Ariane and Salo-Ahen, Outi M H and Herwald, Heiko and Smeds, Emanuel},
  issn         = {1751-7907},
  language     = {eng},
  month        = {02},
  number       = {3},
  pages        = {657--665},
  publisher    = {John Wiley and Sons Ltd},
  series       = {Microbial Biotechnology},
  title        = {A rapid method for selecting suitable animal species for studying pathogen interactions with plasma protein ligands in vivo},
  url          = {http://dx.doi.org/10.1111/1751-7915.12601},
  volume       = {10},
  year         = {2017},
}