TheRickettsia conoriiAutotransporter Protein Sca1 Promotes Adherence to Nonphagocytic Mammalian Cells

Abstract

The pathogenesis of spotted fever group (SFG)Rickettsiaspecies, includingR. conoriiandR. rickettsii, is acutely dependent on adherence to and invasion of host cells, including cells of the mammalian endothelial system. Bioinformatic analyses of several rickettsia genomes revealed the presence of a cohort of genes designatedscagenes that are predicted to encode proteins with homology to autotransporter proteins of Gram-negative bacteria. Previous work demonstrated that three members of this family, rOmpA (Sca0), Sca2, and rOmpB (Sca5) are involved in the interaction with mammalian cells; however, very little was known about the function of other conserved rickettsial Sca proteins. Here we demonstrate thatsca1, a gene present in nearly all SFG rickettsia genomes, is actively transcribed and expressed inR. conoriicells. Alignment of Sca1 sequences from geographically diverse SFGRickettsiaspecies showed that there are high degrees of sequence identity and conservation of these sequences, suggesting that Sca1 may have a conserved function. Using a heterologous expression system, we demonstrated that production ofR. conoriiSca1 in theEscherichia coliouter membrane is sufficient to mediate attachment to but not invasion of a panel of cultured mammalian epithelial and endothelial cells. Furthermore, preincubation of a recombinant Sca1 peptide with host cells blockedR. conoriicell association. Together, these results demonstrate that attachment to mammalian cells can be uncoupled from the entry process and that Sca1 is involved in the adherence ofR. conoriito host cells.