title: The Hd, Hj, and Hz66 flagella variants of Salmonella enterica serovar Typhi modify host responses and cellular interactions.
abstract: Salmonella Typhi, the causative agent of typhoid fever, is a monophyletic, human-restricted bacterium that exhibits limited phenotypic variation. S. Typhi from Indonesia are a notable exception, with circulating strains expressing diverse flagella antigens including Hj, Hd and Hz66. Hypothesizing that S. Typhi flagella plays a key role during infection, we constructed an S. Typhi fliC mutant and otherwise isogenic S. Typhi strains expressing the Hj, Hd, Hz66 flagella antigens. Phenotyping revealed differences in flagellum structure, strain motility and immunogenicity, but not in the ability of flagellated isolates to induce TLR5 activity. Invasion assays using epithelial and macrophage cell lines revealed differences in the ability of these S. Typhi derivatives to invade cells or induce cellular restructuring in the form of ruffles. Notably, the Hj variant induced substantial ruffles that were not fully dependent on the GTPases that contribute to this process. These data highlight important differences in the phenotypic properties of S. Typhi flagella variation and how they impact on the pathogenesis of S. Typhi.
authors.affiliation: The Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Schreiber
authors.affiliation: The Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.
authors.forename: Sally
authors.initials: S
authors.lastname: Kay
authors.affiliation: Centre for Molecular Microbiology and Infection, Imperial College, London, United Kingdom.
authors.forename: Gad
authors.initials: G
authors.lastname: Frankel
authors.affiliation: The Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.
authors.forename: Simon
authors.initials: S
authors.lastname: Clare
authors.affiliation: The Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Goulding
authors.affiliation: Department of Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Esther
authors.initials: E
authors.lastname: van de Vosse
authors.affiliation: Department of Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Jaap T
authors.initials: JT
authors.lastname: van Dissel
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Parkville, Australia.
authors.forename: Richard
authors.initials: R
authors.lastname: Strugnell
authors.affiliation: 1] The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam [2] Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Oxford University, United Kingdom.
authors.forename: Guy
authors.initials: G
authors.lastname: Thwaites
authors.affiliation: Institute for Food Research, Norwich, United Kingdom.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kingsley
authors.affiliation: The Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.
authors.forename: Gordon
authors.initials: G
authors.lastname: Dougan
authors.affiliation: 1] The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam [2] Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Oxford University, United Kingdom [3] The London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Stephen
authors.initials: S
authors.lastname: Baker
mesh_terms: D000942:Antigens, Bacterial / Q000096:biosynthesis* / Q000235:genetics; D001422:Bacterial Adhesion; D002450:Cell Communication / Q000235:genetics*; D005407:Flagella / Q000235:genetics / Q000382:microbiology; D015964:Gene Expression Regulation, Bacterial; D054884:Host-Pathogen Interactions; D006801:Humans; D007214:Indonesia; D008264:Macrophages / Q000382:microbiology; D012485:Salmonella typhi / Q000235:genetics* / Q000472:pathogenicity; D014435:Typhoid Fever / Q000235:genetics* / Q000382:microbiology
chemical_list: D000942:Antigens, Bacterial