title: Tyrosine kinases, drugs, and Shigella flexneri dissemination.
abstract: Shigella flexneri is an enteropathogenic bacterium responsible for approximately 100 million cases of severe dysentery each year. S. flexneri colonization of the human colonic epithelium is supported by direct spread from cell to cell, which relies on actin-based motility. We have recently uncovered that, in intestinal epithelial cells, S. flexneri actin-based motility is regulated by the Bruton's tyrosine kinase (Btk). Consequently, treatment with Ibrutinib, a specific Btk inhibitor currently used in the treatment of B-cell malignancies, effectively impaired S. flexneri spread from cell to cell. Thus, therapeutic intervention capitalizing on drugs interfering with host factors supporting the infection process may represent an effective alternative to treatments with antimicrobial compounds.
authors.affiliation: Department of Microbial Pathogenesis; Boyer Center for Molecular Medicine; Yale School of Medicine; New Haven, CT USA.
authors.forename: Ana-Maria
authors.initials: AM
authors.lastname: Dragoi
authors.affiliation: Department of Microbial Pathogenesis; Boyer Center for Molecular Medicine; Yale School of Medicine; New Haven, CT USA.
authors.forename: Hervé
authors.initials: H
authors.lastname: Agaisse
mesh_terms: D004405:Dysentery, Bacillary / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000382:microbiology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D012763:Shigella flexneri / Q000378:metabolism*
chemical_list: D011505:Protein-Tyrosine Kinases
keywords: Btk; Ibrutinib; N-WASP; Shigella flexneri; actin-based motility; dissemination; phosphorylation; spread from cell to cell; tyrosine kinase