title: Identification of cytokeratins as accessory mediators of Salmonella entry into eukaryotic cells.
abstract: Pathogenic Salmonella species initiate infection of a mammalian host by inducing their own uptake into intestinal M-cells. During the uptake process, the bacteria utilize an intrinsic secretion system to release proteins that enter host cells. The secreted invasion-mediating proteins subsequently interact with host cell components that induce alterations in the actin cytoskeleton. To identify potential cellular determinants of invasion, we employed a yeast two-hybrid system using the secreted Salmonella invasion protein (SipC) as the bait protein. This system identified cytokeratins, supportive components of the cytoskeletal matrix, as proteins that may physically interact with SipC. Transfection-based studies revealed an inhibition of Salmonella invasion when a dominant negative cytokeratin-18 was expressed. Immunofluorescent confocal microscopy studies revealed that Salmonella did not enter HEp-2 cells expressing the dominant negative cytokeratin-18. These results suggest that an interaction between SipC and cytokeratin-18 may occur as part of Salmonella invasion.
authors.affiliation: Preharvest Food Safety and Enteric Disease Research Unit, National Animal Disease Center, USDA, Agricultural Research Service, Ames, IA 50010, USA. scarlson@nadc.ars.usda.gov
authors.forename: Steve A
authors.initials: SA
authors.lastname: Carlson
authors.forename: M Bishr
authors.initials: MB
authors.lastname: Omary
authors.forename: Bradley D
authors.initials: BD
authors.lastname: Jones
mesh_terms: D000199:Actins / Q000648:ultrastructure; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D005057:Eukaryotic Cells / Q000378:metabolism* / Q000382:microbiology; D005656:Fungal Proteins / Q000378:metabolism; D006801:Humans; D007633:Keratins / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D012480:Salmonella Infections / Q000382:microbiology*; D012486:Salmonella typhimurium / Q000145:classification / Q000472:pathogenicity* / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D014774:Virulence / Q000502:physiology
chemical_list: D000199:Actins; D001426:Bacterial Proteins; D005656:Fungal Proteins; D008565:Membrane Proteins; C094578:Salmonella invasion protein C; D014157:Transcription Factors; D007633:Keratins