title: The role of flagella and chemotaxis genes in host pathogen interaction of the host adapted Salmonella enterica serovar Dublin compared to the broad host range serovar S. Typhimurium.
abstract: BACKGROUND
  The importance of flagella and chemotaxis genes in host pathogen interaction in Salmonella enterica is mainly based on studies of the broad host range serovar, S. Typhimurium, while little is known on the importance in host specific and host adapted serovars, such as S. Dublin. In the current study we have used previously characterized insertion mutants in flagella and chemotaxis genes to investigate this and possible differences in the importance between the two serovars.
  
  
  RESULTS
  fliC (encoding the structural protein of the flagella) was essential for adhesion and fliC and cheB (CheB restores the chemotaxis system to pre-stimulus conformation) were essential for invasion of S. Dublin into epithelial Int407 cells. In S. Typhimurium, both lack of flagella (fliC/fljB double mutant) and cheB influenced adhesion, and invasion was influenced by lack of both cheA (the histidine-kinase of the chemotaxis system), fliC/fljB and cheB mutation. Uptake in J774A.1 macrophage cells was significantly reduced in cheA, cheB and fliC mutants of S. Dublin, while cheA was dispensable in S. Typhimurium. Removal of flagella in both serotypes caused an increased ability to propagate intracellular in J774 macrophage cells and decreased cytotoxicity toward these cells. Flagella and chemotaxis genes were found not to influence the oxidative response. The induction of IL-6 from J774A-1 cells depended on the presence of flagella in S. Typhimurium, whilst this was not the case following challenge with S. Dublin. Addition of fliC from S. Typhimurium in trans to a fliC mutant of S. Dublin increased cytotoxicity but it did not increase the IL-6 production. Flagella were demonstrated to contribute to the outcome of infection following oral challenge of mice in S. Dublin, while an S. Typhimurium fliC/fljB mutant showed increased virulence following intra peritoneal challenge.
  
  
  CONCLUSIONS
  The results showed that flagella and chemotaxis genes differed in their role in host pathogen interaction between S. Dublin and S. Typhimurium. Notably, lack of flagella conferred a more virulent phenotype in S. Typhimurium at systemic sites, while this was not the case in S. Dublin. In vitro assays suggested that this could be related to flagella-induced induction of the IL-6 pro-inflammatory response, but further in vivo studies are needed to confirm this.
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Stigbøjlen 4, 1870 Frederiksberg C, Denmark. jeo@sund.ku.dk
authors.forename: John Elmerdahl
authors.initials: JE
authors.lastname: Olsen
authors.forename: Kirsten Hobolt
authors.initials: KH
authors.lastname: Hoegh-Andersen
authors.forename: Josep
authors.initials: J
authors.lastname: Casadesús
authors.forename: Jesper
authors.initials: J
authors.lastname: Rosenkranzt
authors.forename: Mark Simon
authors.initials: MS
authors.lastname: Chadfield
authors.forename: Line Elnif
authors.initials: LE
authors.lastname: Thomsen
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion; D002460:Cell Line; D002633:Chemotaxis; D004705:Endocytosis; D004847:Epithelial Cells / Q000382:microbiology; D005260:Female; D005407:Flagella / Q000502:physiology*; D054884:Host-Pathogen Interactions; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D016254:Mutagenesis, Insertional; D019779:Salmonella enterica / Q000472:pathogenicity* / Q000502:physiology; D014774:Virulence