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

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Author

Summary, in English

. 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.

Publishing year

2016-03-15

Language

English

Pages

504-516

Publication/Series

International Journal of Medical Microbiology

Volume

306

Issue

7

Document type

Journal article

Publisher

Elsevier

Topic

  • Microbiology in the medical area

Keywords

  • Host adaptation
  • Pathogenesis
  • Proteomics
  • Streptococcus pyogenes

Status

Published

Project

  • Proteomic profiling of bacterial host adaptation - Racing the Red Queen

Research group

  • Infection Medicine Proteomics

ISBN/ISSN/Other

  • ISSN: 1438-4221