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Virulence of Group A Streptococci Is Enhanced by Human Complement Inhibitors


Streptococcus pyogenes is an important cause of human infections worldwide, ranging from mild and superficial disease to life-threatening invasive infections. Development of new and efficient therapies for infections requires animal models that faithfully recapitulate infection in humans. Humans are the only natural host of S. pyogenes; thus, infection in wild-type mice may not reflect infection in humans. Mice that are humanized in ways that are relevant to the studied pathogen would better reproduce human infection. Because S. pyogenes bind only human, but not mouse complement inhibitors, we used novel strains of humanized mice that produce two human complement inhibitory proteins which allowed us to analyze the impact of human-specific human complement inhibition on the severity of S. pyogenes infections in mice. Here, we show that expression of human complement inhibitors significantly worsens the outcome of infection in humanized mice. This animal model will permit studies of infection and disease and aid the development of novel therapies and vaccines against S. pyogenes infections, with emphasis on the human complement system.


Vyšlo v časopise: Virulence of Group A Streptococci Is Enhanced by Human Complement Inhibitors. PLoS Pathog 11(7): e32767. doi:10.1371/journal.ppat.1005043
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005043

Souhrn

Streptococcus pyogenes is an important cause of human infections worldwide, ranging from mild and superficial disease to life-threatening invasive infections. Development of new and efficient therapies for infections requires animal models that faithfully recapitulate infection in humans. Humans are the only natural host of S. pyogenes; thus, infection in wild-type mice may not reflect infection in humans. Mice that are humanized in ways that are relevant to the studied pathogen would better reproduce human infection. Because S. pyogenes bind only human, but not mouse complement inhibitors, we used novel strains of humanized mice that produce two human complement inhibitory proteins which allowed us to analyze the impact of human-specific human complement inhibition on the severity of S. pyogenes infections in mice. Here, we show that expression of human complement inhibitors significantly worsens the outcome of infection in humanized mice. This animal model will permit studies of infection and disease and aid the development of novel therapies and vaccines against S. pyogenes infections, with emphasis on the human complement system.


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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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