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Differential compartmentalization of Streptococcus pyogenes virulence factors and host protein binding properties as a mechanism for host adaptation

Kilsgård, Ola LU ; Karlsson, Christofer LU ; Malmström, Erik LU and Malmström, Johan LU (2016) In International Journal of Medical Microbiology 306(7). p.504-516
Abstract

. Streptococcus pyogenes is an important human pathogen responsible for substantial morbidity and mortality worldwide. Although . S. pyogenes is a strictly human pathogen with no other known animal reservoir, several murine infection models exist to explore different aspects of the bacterial pathogenesis. Inoculating mice with wild-type . S. pyogenes strains can result in the generation of new bacterial phenotypes that are hypervirulent compared to the original inoculum. In this study, we used a serial mass spectrometry based proteomics strategy to investigate if these hypervirulent strains have an altered distribution of virulence proteins across the intracellular, surface associated and secreted bacterial compartments and if any... (More)

. Streptococcus pyogenes is an important human pathogen responsible for substantial morbidity and mortality worldwide. Although . S. pyogenes is a strictly human pathogen with no other known animal reservoir, several murine infection models exist to explore different aspects of the bacterial pathogenesis. Inoculating mice with wild-type . S. pyogenes strains can result in the generation of new bacterial phenotypes that are hypervirulent compared to the original inoculum. In this study, we used a serial mass spectrometry based proteomics strategy to investigate if these hypervirulent strains have an altered distribution of virulence proteins across the intracellular, surface associated and secreted bacterial compartments and if any change in compartmentalization can alter the protein-protein interaction network between bacteria and host proteins. Quantitative analysis of the . S. pyogenes surface and secreted proteomes revealed that animal passaged strains are associated with significantly higher amount of virulence factors on the bacterial surface and in the media. This altered virulence factor compartmentalization results in increased binding of several mouse plasma proteins to the bacterial surface, a trend that was consistent for mouse plasma from several different mouse strains. In general, both the wild-type strain and animal passaged strain were capable of binding high amounts of human plasma proteins. However, compared to the non-passaged strains, the animal passaged strains displayed an increased ability to bind mouse plasma proteins, in particular for M protein binders, indicating that the increased affinity for mouse blood plasma proteins is a consequence of host adaptation of this pathogen to a new host. In conclusion, plotting the total amount of virulence factors against the total amount of plasma proteins associated to the bacterial surface could clearly separate out animal passaged strains from wild type strains indicating a virulence model that could predict the virulence of a . S. pyogenes strain in mice and which could be used to identify key aspects of this bacteria's pathogenesis.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Host adaptation, Pathogenesis, Proteomics, Streptococcus pyogenes
in
International Journal of Medical Microbiology
volume
306
issue
7
pages
504 - 516
publisher
Elsevier
external identifiers
  • Scopus:84979519861
ISSN
1438-4221
DOI
10.1016/j.ijmm.2016.06.007
language
English
LU publication?
yes
id
2a3956b0-33ef-4527-a4d8-d374d944787d
date added to LUP
2016-09-08 15:58:46
date last changed
2017-01-03 15:15:25
@article{2a3956b0-33ef-4527-a4d8-d374d944787d,
  abstract     = {<p>. Streptococcus pyogenes is an important human pathogen responsible for substantial morbidity and mortality worldwide. Although . S. pyogenes is a strictly human pathogen with no other known animal reservoir, several murine infection models exist to explore different aspects of the bacterial pathogenesis. Inoculating mice with wild-type . S. pyogenes strains can result in the generation of new bacterial phenotypes that are hypervirulent compared to the original inoculum. In this study, we used a serial mass spectrometry based proteomics strategy to investigate if these hypervirulent strains have an altered distribution of virulence proteins across the intracellular, surface associated and secreted bacterial compartments and if any change in compartmentalization can alter the protein-protein interaction network between bacteria and host proteins. Quantitative analysis of the . S. pyogenes surface and secreted proteomes revealed that animal passaged strains are associated with significantly higher amount of virulence factors on the bacterial surface and in the media. This altered virulence factor compartmentalization results in increased binding of several mouse plasma proteins to the bacterial surface, a trend that was consistent for mouse plasma from several different mouse strains. In general, both the wild-type strain and animal passaged strain were capable of binding high amounts of human plasma proteins. However, compared to the non-passaged strains, the animal passaged strains displayed an increased ability to bind mouse plasma proteins, in particular for M protein binders, indicating that the increased affinity for mouse blood plasma proteins is a consequence of host adaptation of this pathogen to a new host. In conclusion, plotting the total amount of virulence factors against the total amount of plasma proteins associated to the bacterial surface could clearly separate out animal passaged strains from wild type strains indicating a virulence model that could predict the virulence of a . S. pyogenes strain in mice and which could be used to identify key aspects of this bacteria's pathogenesis.</p>},
  author       = {Kilsgård, Ola and Karlsson, Christofer and Malmström, Erik and Malmström, Johan},
  issn         = {1438-4221},
  keyword      = {Host adaptation,Pathogenesis,Proteomics,Streptococcus pyogenes},
  language     = {eng},
  month        = {03},
  number       = {7},
  pages        = {504--516},
  publisher    = {Elsevier},
  series       = {International Journal of Medical Microbiology},
  title        = {Differential compartmentalization of Streptococcus pyogenes virulence factors and host protein binding properties as a mechanism for host adaptation},
  url          = {http://dx.doi.org/10.1016/j.ijmm.2016.06.007},
  volume       = {306},
  year         = {2016},
}