The adherens junctions control susceptibility to staphylococcus aureus α-toxin
Abstract/Contents
- Abstract
- Staphylococcus aureus is both a transient skin colonizer and a formidable human pathogen, ranking among the leading causes of skin and soft tissue infections as well as severe pneumonia. The secreted bacterial alpha-toxin is essential for S. aureus virulence in these epithelial diseases. To discover host cellular factors required for alpha-toxin cytotoxicity, we conducted a genetic screen using mutagenized haploid human cells. Our screen identified a cytoplasmic member of the adherens junctions, plekstrin-homology domain containing protein 7 (PLEKHA7), as the second most significantly enriched gene after the known alpha-toxin receptor, a disintegrin and metalloprotease 10 (ADAM10). Here we report a new, unexpected role for PLEKHA7 and several components of cellular adherens junctions in controlling susceptibility to S. aureus alpha-toxin. We find that despite being injured by alpha-toxin pore formation, PLEKHA7 knockout cells recover after intoxication. By infecting PLEKHA7−/− mice with methicillin-resistant S. aureus USA300 LAC strain, we demonstrate that this junctional protein controls disease severity in both skin infection and lethal S. aureus pneumonia. Our results suggest that adherens junctions actively control cellular responses to a potent pore-forming bacterial toxin and identify PLEKHA7 as a potential non-essential host target to reduce S. aureus virulence during epithelial infections.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2016 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Popov, Lauren Marie |
|---|---|
| Associated with | Stanford University, Department of Microbiology and Immunology. |
| Primary advisor | Amieva, Manuel |
| Thesis advisor | Amieva, Manuel |
| Thesis advisor | Falkow, Stanley |
| Thesis advisor | Monack, Denise M |
| Thesis advisor | Relman, David A |
| Advisor | Falkow, Stanley |
| Advisor | Monack, Denise M |
| Advisor | Relman, David A |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Lauren Marie Popov. |
|---|---|
| Note | Submitted to the Department of Microbiology and Immunology. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2016. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2016 by Lauren Marie Popov
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
Also listed in
Loading usage metrics...