title: Shigella enterotoxin-2 is a type III effector that participates in Shigella-induced interleukin 8 secretion by epithelial cells.
abstract: We have previously described a protein termed Shigella enterotoxin 2 (ShET-2), which induces rises in short-circuit current in rabbit ileum mounted in the Ussing chamber. Published reports have postulated that ShET-2 may be secreted by the Shigella type III secretion system (T3SS). In this study, we show that ShET-2 secretion into the extracellular space requires the T3SS in Shigella flexneri 2a strain 2457T and a ShET-2-TEM fusion was translocated into epithelial cells in a T3SS-dependent manner. The ShET-2 gene, sen, is encoded downstream of the ospC1 gene of S. flexneri, and we show that sen is cotranscribed with this T3SS-secreted product. Considering that T3SS effectors have diverse roles in Shigella infection and that vaccine constructs lacking ShET-2 are attenuated in volunteers, we asked whether ShET-2 has a function other than its enterotoxic activity. We constructed a ShET-2 mutant in 2457T and tested its effect on epithelial cell invasion, plaque formation, guinea pig keratoconjunctivitis and interleukin 8 (IL-8) secretion from infected monolayers. Although other phenotypes were not different compared with the wild-type parent, we found that HEp-2 and T84 cells infected with the ShET-2 mutant exhibited significantly reduced IL-8 secretion into the basolateral compartment, suggesting that ShET-2 might participate in the Shigella-induced inflammation of epithelial cells.
authors.affiliation: Centro de Estudios Moleculares, Departamento de Pediatría, Hospital Luis Calvo Mackennna, Facultad de Medicina, Universidad de Chile, Santiago, Chile. mfarfan@med.uchile.cl
authors.forename: Mauricio J
authors.initials: MJ
authors.lastname: Farfán
authors.forename: Cecilia S
authors.initials: CS
authors.lastname: Toro
authors.forename: Eileen M
authors.initials: EM
authors.lastname: Barry
authors.forename: James P
authors.initials: JP
authors.lastname: Nataro
mesh_terms: D000818:Animals; D002460:Cell Line; D004768:Enterotoxins / Q000378:metabolism* / Q000633:toxicity*; D004847:Epithelial Cells / Q000276:immunology / Q000382:microbiology*; D006801:Humans; D016209:Interleukin-8 / Q000276:immunology* / Q000378:metabolism*; D021381:Protein Transport; D012763:Shigella flexneri / Q000276:immunology* / Q000472:pathogenicity*
chemical_list: D004768:Enterotoxins; D016209:Interleukin-8