Article ; Online: Streptolysin S is required for Streptococcus pyogenes nasopharyngeal and skin infection in HLA-transgenic mice.
2024 Volume 20, Issue 3, Page(s) e1012072
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 ... ...
| 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. |
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| MeSH term(s) | Humans ; Mice ; Animals ; Streptococcus pyogenes/metabolism ; Streptolysins/genetics ; Streptolysins/metabolism ; Mice, Transgenic ; Streptococcal Infections/metabolism ; Bacterial Proteins/metabolism ; Nasopharynx |
| Chemical Substances | Streptolysins ; Bacterial Proteins |
| Language | English |
| Publishing date | 2024-03-07 |
| Publishing country | United States |
| Document type | Journal Article |
| ZDB-ID | 2205412-1 |
| ISSN | 1553-7374 ; 1553-7374 |
| ISSN (online) | 1553-7374 |
| ISSN | 1553-7374 |
| DOI | 10.1371/journal.ppat.1012072 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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