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Streptolysin S is required for Streptococcus pyogenes nasopharyngeal and skin infection in HLA-transgenic mice
Blake A Shannon1, Jacklyn R Hurst1, Ronald S Flannagan1
1Department of Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada.
Abstract:
Streptococcus pyogenes is a human-specific pathogen that commonly colonizes the upper respiratory tract and skin, causing a wide variety of diseases ranging from pharyngitis to necrotizing fasciitis and toxic shock syndrome. S. pyogenes has a repertoire of secreted virulence factors that promote infection and evasion of the host immune system including the cytolysins streptolysin O (SLO) and streptolysin S (SLS). S. pyogenes does not naturally infect the upper respiratory tract of mice although mice transgenic for MHC class II human leukocyte antigens (HLA) become highly susceptible. Here we used HLA-transgenic mice to assess the role of both SLO and SLS during both nasopharyngeal and skin infection. Using S. pyogenes MGAS8232 as a model strain, we found that an SLS-deficient strain exhibited a 100-fold reduction in bacterial recovery from the nasopharynx and a 10-fold reduction in bacterial burden in the skin, whereas an SLO-deficient strain did not exhibit any infection defects in these models. Furthermore, depletion of neutrophils significantly restored the bacterial burden of the SLS-deficient bacteria in skin, but not in the nasopharynx. In mice nasally infected with the wildtype S. pyogenes, there was a marked change in localization of the tight junction protein ZO-1 at the site of infection, demonstrating damage to the nasal epithelia that was absent in mice infected with the SLS-deficient strain. Overall, we conclude that SLS is required for the establishment of nasopharyngeal infection and skin infection in HLA-transgenic mice by S. pyogenes MGAS8232 and provide evidence that SLS contributes to nasopharyngeal infection through the localized destruction of nasal epithelia.
Insights
Streptococcus pyogenes relies on streptolysin S (SLS) for nasopharyngeal and skin infections in HLA-transgenic mice. SLS damages nasal epithelia, while streptolysin O (SLO) plays no significant role in these models.
Area of Science:
- Microbiology
- Immunology
- Pathogenesis
Background:
- Streptococcus pyogenes is a human pathogen causing diverse infections.
- Virulence factors like streptolysin O (SLO) and streptolysin S (SLS) aid S. pyogenes infection and immune evasion.
- Mice transgenic for human leukocyte antigens (HLA) are susceptible to S. pyogenes nasopharyngeal and skin infections.
Purpose of the Study:
- To investigate the roles of SLO and SLS in S. pyogenes nasopharyngeal and skin infections using HLA-transgenic mice.
- To elucidate the mechanisms by which SLS contributes to infection, particularly epithelial damage.
Main Methods:
- Utilized HLA-transgenic mice to model S. pyogenes infections.
- Compared infection outcomes between wildtype, SLS-deficient, and SLO-deficient S. pyogenes strains.
- Assessed bacterial burden in nasopharyngeal and skin sites.
- Investigated the impact of neutrophil depletion on infection.
- Examined the localization of the tight junction protein ZO-1 in nasal epithelia.
Main Results:
- SLS-deficient S. pyogenes showed significantly reduced bacterial recovery from the nasopharynx (100-fold) and skin (10-fold).
- SLO-deficient S. pyogenes did not exhibit any infection defects.
- Neutrophil depletion partially restored skin bacterial burden but not nasopharyngeal burden for SLS-deficient bacteria.
- Wildtype S. pyogenes infection caused nasal epithelial damage (ZO-1 relocalization), which was absent in infections with SLS-deficient strains.
Conclusions:
- SLS is essential for the establishment of both nasopharyngeal and skin infections by S. pyogenes MGAS8232 in HLA-transgenic mice.
- SLS contributes to nasopharyngeal infection by causing localized damage to nasal epithelia.
- SLO is not required for these specific infection models.
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