title: Flagellin phase-dependent swimming on epithelial cell surfaces contributes to productive Salmonella gut colonisation.
abstract: The flagellum is a sophisticated nanomachine and an important virulence factor of many pathogenic bacteria. Flagellar motility enables directed movements towards host cells in a chemotactic process, and near-surface swimming on cell surfaces is crucial for selection of permissive entry sites. The long external flagellar filament is made of tens of thousands subunits of a single protein, flagellin, and many Salmonella serovars alternate expression of antigenically distinct flagellin proteins, FliC and FljB. However, the role of the different flagellin variants during gut colonisation and host cell invasion remains elusive. Here, we demonstrate that flagella made of different flagellin variants display structural differences and affect Salmonella's swimming behaviour on host cell surfaces. We observed a distinct advantage of bacteria expressing FliC-flagella to identify target sites on host cell surfaces and to invade epithelial cells. FliC-expressing bacteria outcompeted FljB-expressing bacteria for intestinal tissue colonisation in the gastroenteritis and typhoid murine infection models. Intracellular survival and responses of the host immune system were not altered. We conclude that structural properties of flagella modulate the swimming behaviour on host cell surfaces, which facilitates the search for invasion sites and might constitute a general mechanism for productive host cell invasion of flagellated bacteria.
authors.affiliation: Junior Research Group Infection Biology of Salmonella, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Julia A
authors.identifier: 0000-0002-1368-1795
authors.initials: JA
authors.lastname: Horstmann
authors.affiliation: Department for Structural Infection Biology, Center for Structural Systems Biology, Hamburg, Germany.|Department for Structural Infection Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Erik
authors.initials: E
authors.lastname: Zschieschang
authors.affiliation: InSCREENeX GmbH, Braunschweig, Germany.
authors.forename: Theresa
authors.initials: T
authors.lastname: Truschel
authors.affiliation: Department for Structural Infection Biology, Center for Structural Systems Biology, Hamburg, Germany.|Department for Structural Infection Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Juana
authors.initials: J
authors.lastname: de Diego
authors.affiliation: Department for Structural Infection Biology, Center for Structural Systems Biology, Hamburg, Germany.|Department for Structural Infection Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Michele
authors.initials: M
authors.lastname: Lunelli
authors.affiliation: Central Facility for Microscopy, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Rohde
authors.affiliation: InSCREENeX GmbH, Braunschweig, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: May
authors.affiliation: Junior Research Group Microbial Immune Regulation, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Till
authors.initials: T
authors.lastname: Strowig
authors.affiliation: Department of Cell Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Theresia
authors.initials: T
authors.lastname: Stradal
authors.affiliation: Department for Structural Infection Biology, Center for Structural Systems Biology, Hamburg, Germany.|Department for Structural Infection Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany.|MIN-Faculty University Hamburg, Hamburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Kolbe
authors.affiliation: Junior Research Group Infection Biology of Salmonella, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Marc
authors.identifier: 0000-0001-6292-619X
authors.initials: M
authors.lastname: Erhardt
mesh_terms: D000818:Animals; D004847:Epithelial Cells / Q000382:microbiology*; D005408:Flagellin / Q000378:metabolism*; D041981:Gastrointestinal Tract / Q000382:microbiology*; D008124:Locomotion; D051379:Mice; D012475:Salmonella / Q000502:physiology*; D012481:Salmonella Infections, Animal / Q000382:microbiology
chemical_list: D005408:Flagellin
keywords: Salmonella; flagella phase variation; flagellin; motility; near-surface swimming