An Autotransporter Protein fromOrientia tsutsugamushiMediates Adherence to Nonphagocytic Host Cells
ABSTRACTOrientia tsutsugamushi, the causative agent of scrub typhus, is an obligate intracellular pathogen whose mechanism of cellular adhesion and invasion is poorly characterized. Bioinformatic analyses of twoO. tsutsugamushigenomes revealed the presence of a group of genes that encode autotransporter proteins. In this study, we identified 10 autotransporter gene products and categorized them into five groups of orthologs (ScaA to ScaE) based on their sequence similarities. Sequence homology was highest between members of ScaC group, suggesting the functional conservation of bacterium-host interactions. ScaC was actively expressed on the surface ofO. tsutsugamushiand induced antibody responses in scrub typhus patients. Experiments using microbeads conjugated to recombinant ScaC or a surrogateEscherichia coliexpression system showed that ScaC was sufficient to mediate attachment to, but not invasion of, nonphagocytic mammalian cells. In addition, preincubation of host cells with recombinant ScaC significantly inhibited their interaction withO. tsutsugamushi. Finally, fibronectin was identified as a potential receptor for ScaC by using yeast two-hybrid screening, and this was confirmed using a glutathioneS-transferase (GST) pulldown assay. Taken together, these results demonstrate that ScaC is involved in the interaction ofO. tsutsugamushiwith mammalian host cells and suggest that ScaC may play a critical role in bacterial pathogenesis.