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Published on: February 19, 2019
Differential compartmentalization of Streptococcus pyogenes virulence factors and host protein binding properties as
Ola Kilsgård1, Christofer Karlsson2, Erik Malmström2
1Division of Infection Medicine, Department of Clinical Sciences Lund, Lund University, Lund, Sweden; Department of Immunotechnology, Faculty of Engineering Lund, Lund University, Lund, Sweden.
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 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.
Insights
Streptococcus pyogenes adapted to mice by increasing surface virulence factors, enhancing mouse plasma protein binding. This adaptation offers a model to predict bacterial virulence and understand pathogenesis in new hosts.
Area of Science:
- Microbiology
- Pathogenesis
- Proteomics
Background:
- Streptococcus pyogenes is a significant human pathogen causing widespread disease.
- Murine models are used to study S. pyogenes pathogenesis, sometimes yielding hypervirulent strains.
- Host adaptation and altered virulence factor distribution in these strains are not fully understood.
Purpose of the Study:
- To investigate if hypervirulent S. pyogenes strains exhibit altered virulence protein distribution across bacterial compartments.
- To determine if changes in protein compartmentalization affect interactions with host proteins.
- To explore host adaptation mechanisms in S. pyogenes using murine models.
Main Methods:
- Serial mass spectrometry-based proteomics was employed.
- Quantitative analysis of surface-associated and secreted S. pyogenes proteomes.
- Assessment of bacterial binding to mouse and human plasma proteins.
Main Results:
- Animal-passaged S. pyogenes strains showed significantly higher surface and secreted levels of virulence factors.
- These adapted strains exhibited increased binding of mouse plasma proteins, particularly M protein binders.
- A correlation between virulence factor load and plasma protein association could distinguish adapted from wild-type strains.
Conclusions:
- Host adaptation of S. pyogenes to murine models involves increased surface virulence factors and enhanced mouse plasma protein affinity.
- Altered virulence factor compartmentalization is a key feature of hypervirulent strains.
- A model correlating virulence factors and plasma protein binding may predict S. pyogenes virulence and identify pathogenic mechanisms.
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