The Hd, Hj, and Hz66 flagella variants of Salmonella enterica serovar Typhi modify host responses and cellular interactions
Schreiber F., Kay S., Frankel G., Clare S., Goulding D., van de Vosse E., van Dissel JT., Strugnell R., Thwaites G., Kingsley RA., Dougan G., Baker S.
AbstractSalmonellaTyphi, 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,Hdand Hz66. Hypothesizing thatS. Typhi flagella plays a key role during infection, we constructed anS. TyphifliCmutant and otherwise isogenicS. Typhi strains expressing the Hj,Hd, Hz66flagella 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 theseS. Typhi derivatives to invade cells or induce cellular restructuring in the form of ruffles. Notably, the Hjvariant 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 ofS. Typhi flagella variation and how they impact on the pathogenesis ofS. Typhi.