Proceedings of the National Academy of Sciences - PNAS, 2015-11, Vol.112 (46), p.14337-14342
2015
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- Autor(en) / Beteiligte
- Titel
- The adherens junctions control susceptibility to Staphylococcus aureus α-toxin
- Ist Teil von
- Proceedings of the National Academy of Sciences - PNAS, 2015-11, Vol.112 (46), p.14337-14342
- Ort / Verlag
- United States: National Acad Sciences
- Erscheinungsjahr
- 2015
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- 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 α-toxin is essential for S. aureus virulence in these epithelial diseases. To discover host cellular factors required for α-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 α-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 α-toxin. We find that despite being injured by α-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 nonessential host target to reduce S. aureus virulence during epithelial infections.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0027-8424eISSN: 1091-6490DOI: 10.1073/pnas.1510265112Titel-ID: cdi_proquest_miscellaneous_1762377916
- Format
- –
- Schlagworte
- ADAM Proteins - genetics, ADAM Proteins - metabolism, ADAM10 Protein, Adherens Junctions - genetics, Adherens Junctions - metabolism, Amyloid Precursor Protein Secretases - genetics, Amyloid Precursor Protein Secretases - metabolism, Animals, Bacterial Toxins - genetics, Bacterial Toxins - metabolism, Biological Sciences, Carrier Proteins - genetics, Carrier Proteins - metabolism, Cell Line, Hemolysin Proteins - genetics, Hemolysin Proteins - metabolism, Humans, Membrane Proteins - genetics, Membrane Proteins - metabolism, Methicillin-Resistant Staphylococcus aureus - genetics, Methicillin-Resistant Staphylococcus aureus - metabolism, Methicillin-Resistant Staphylococcus aureus - pathogenicity, Mice, Mice, Knockout, Staphylococcal Infections - genetics, Staphylococcal Infections - metabolism, Staphylococcal Infections - pathology, Staphylococcus aureus, Vasculitis - genetics, Vasculitis - metabolism, Vasculitis - microbiology, Vasculitis - pathology