Correlation Engine 2.0
Clear Search sequence regions


Sizes of these terms reflect their relevance to your search.

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.

Citation

Lauren M Popov, Caleb D Marceau, Philipp M Starkl, Jennifer H Lumb, Jimit Shah, Diego Guerrera, Rachel L Cooper, Christina Merakou, Donna M Bouley, Wenxiang Meng, Hiroshi Kiyonari, Masatoshi Takeichi, Stephen J Galli, Fabio Bagnoli, Sandra Citi, Jan E Carette, Manuel R Amieva. The adherens junctions control susceptibility to Staphylococcus aureus α-toxin. Proceedings of the National Academy of Sciences of the United States of America. 2015 Nov 17;112(46):14337-42

Expand section icon Mesh Tags

Expand section icon Substances


PMID: 26489655

View Full Text