S. aureus virulence factors decrease epithelial barrier function and increase susceptibility to viral infection
ABSTRACT Individuals with atopic dermatitis (AD) are highly colonized by Staphylococcus aureus and are more susceptible to severe viral complications. We hypothesized that S. aureus secreted virulence factors may alter keratinocyte biology to enhance viral susceptibility through disruption of the sk...
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2023-10-01
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| Series: | Microbiology Spectrum |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.01684-23 |
| _version_ | 1797658160982392832 |
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| author | Mary C. Moran Matthew G. Brewer Patrick M. Schlievert Lisa A. Beck |
| author_facet | Mary C. Moran Matthew G. Brewer Patrick M. Schlievert Lisa A. Beck |
| author_sort | Mary C. Moran |
| collection | DOAJ |
| description | ABSTRACT Individuals with atopic dermatitis (AD) are highly colonized by Staphylococcus aureus and are more susceptible to severe viral complications. We hypothesized that S. aureus secreted virulence factors may alter keratinocyte biology to enhance viral susceptibility through disruption of the skin barrier, impaired keratinocyte differentiation, and/or inflammation. To address this hypothesis, human keratinocytes were exposed to conditioned media from multiple S. aureus strains that vary in virulence factor production (USA300, HG003, and RN4220) or select purified virulence factors. We have identified the S. aureus enterotoxin-like superantigen SElQ, as a virulence factor of interest, since it is highly produced by USA300 and was detected on the skin of 53% of AD subjects (n = 72) in a study conducted by our group. Treatment with USA300 conditioned media or purified SElQ resulted in a significant increase in keratinocyte susceptibility to infection with vaccinia virus, and also significantly decreased barrier function. Importantly, we have previously demonstrated that keratinocyte differentiation influences susceptibility to viral infection, and our qPCR observations indicated that USA300 S. aureus and SElQ alter differentiation in keratinocytes. CRISPR/Cas9 was used to knock out CD40, a potential enterotoxin receptor on epithelial cells. We found that CD40 expression on keratinocytes was not completely necessary for SElQ-mediated responses, as measured by proinflammatory cytokine expression and barrier function. Together, these findings support that select S. aureus virulence factors, particularly SElQ, enhance the susceptibility of epidermal cells to viral infection, which may contribute to the increased cutaneous infections observed in individuals with AD. Importance Staphylococcus aureus skin colonization and infection are frequently observed in individuals with atopic dermatitis. Many S. aureus strains belong to the clonal group USA300, and these strains produce superantigens including the staphylococcal enterotoxin-like Q (SElQ). Our studies highlight that SElQ may play a key role by altering keratinocyte differentiation and reducing barrier function; collectively, this may explain the AD-specific enhanced infection risk to cutaneous viruses. It is unclear what receptor mediates SElQ’s effects on keratinocytes. We have shown that one putative surface receptor, CD40, was not critical for its effects on proinflammatory cytokine production or barrier function. |
| first_indexed | 2024-03-11T17:56:11Z |
| format | Article |
| id | doaj.art-78bdc464fe7e4a1b8659ea53b1a130e2 |
| institution | Directory Open Access Journal |
| issn | 2165-0497 |
| language | English |
| last_indexed | 2024-03-11T17:56:11Z |
| publishDate | 2023-10-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj.art-78bdc464fe7e4a1b8659ea53b1a130e22023-10-17T13:04:36ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972023-10-0111510.1128/spectrum.01684-23S. aureus virulence factors decrease epithelial barrier function and increase susceptibility to viral infectionMary C. Moran0Matthew G. Brewer1Patrick M. Schlievert2Lisa A. Beck3Department of Dermatology, University of Rochester Medical Center , Rochester, New York, USADepartment of Dermatology, University of Rochester Medical Center , Rochester, New York, USADepartment of Microbiology & Immunology, University of Iowa , Iowa City, Iowa, USADepartment of Dermatology, University of Rochester Medical Center , Rochester, New York, USAABSTRACT Individuals with atopic dermatitis (AD) are highly colonized by Staphylococcus aureus and are more susceptible to severe viral complications. We hypothesized that S. aureus secreted virulence factors may alter keratinocyte biology to enhance viral susceptibility through disruption of the skin barrier, impaired keratinocyte differentiation, and/or inflammation. To address this hypothesis, human keratinocytes were exposed to conditioned media from multiple S. aureus strains that vary in virulence factor production (USA300, HG003, and RN4220) or select purified virulence factors. We have identified the S. aureus enterotoxin-like superantigen SElQ, as a virulence factor of interest, since it is highly produced by USA300 and was detected on the skin of 53% of AD subjects (n = 72) in a study conducted by our group. Treatment with USA300 conditioned media or purified SElQ resulted in a significant increase in keratinocyte susceptibility to infection with vaccinia virus, and also significantly decreased barrier function. Importantly, we have previously demonstrated that keratinocyte differentiation influences susceptibility to viral infection, and our qPCR observations indicated that USA300 S. aureus and SElQ alter differentiation in keratinocytes. CRISPR/Cas9 was used to knock out CD40, a potential enterotoxin receptor on epithelial cells. We found that CD40 expression on keratinocytes was not completely necessary for SElQ-mediated responses, as measured by proinflammatory cytokine expression and barrier function. Together, these findings support that select S. aureus virulence factors, particularly SElQ, enhance the susceptibility of epidermal cells to viral infection, which may contribute to the increased cutaneous infections observed in individuals with AD. Importance Staphylococcus aureus skin colonization and infection are frequently observed in individuals with atopic dermatitis. Many S. aureus strains belong to the clonal group USA300, and these strains produce superantigens including the staphylococcal enterotoxin-like Q (SElQ). Our studies highlight that SElQ may play a key role by altering keratinocyte differentiation and reducing barrier function; collectively, this may explain the AD-specific enhanced infection risk to cutaneous viruses. It is unclear what receptor mediates SElQ’s effects on keratinocytes. We have shown that one putative surface receptor, CD40, was not critical for its effects on proinflammatory cytokine production or barrier function.https://journals.asm.org/doi/10.1128/spectrum.01684-23Staphylococcus aureusatopic dermatitiskeratinocytesviral infectionsuperantigensbarrier function |
| spellingShingle | Mary C. Moran Matthew G. Brewer Patrick M. Schlievert Lisa A. Beck S. aureus virulence factors decrease epithelial barrier function and increase susceptibility to viral infection Microbiology Spectrum Staphylococcus aureus atopic dermatitis keratinocytes viral infection superantigens barrier function |
| title | S. aureus virulence factors decrease epithelial barrier function and increase susceptibility to viral infection |
| title_full | S. aureus virulence factors decrease epithelial barrier function and increase susceptibility to viral infection |
| title_fullStr | S. aureus virulence factors decrease epithelial barrier function and increase susceptibility to viral infection |
| title_full_unstemmed | S. aureus virulence factors decrease epithelial barrier function and increase susceptibility to viral infection |
| title_short | S. aureus virulence factors decrease epithelial barrier function and increase susceptibility to viral infection |
| title_sort | s aureus virulence factors decrease epithelial barrier function and increase susceptibility to viral infection |
| topic | Staphylococcus aureus atopic dermatitis keratinocytes viral infection superantigens barrier function |
| url | https://journals.asm.org/doi/10.1128/spectrum.01684-23 |
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