Chapter 4 : Invasion of the Mammalian Host: Early Events at the Cellular and Molecular Levels

Abstract:

The majority of species belonging to the genus Rickettsia are divided into two groups, the spotted fever group rickettsiae (SFGR) and typhus group rickettsiae (TGR), based on the diseases that they cause, the presence of major surface antigens, and the ability to promote intracellular actin-based motility. This chapter focuses on the cell biology involved in the internalization of SFGR into nonphagocytic mammalian cells using Rickettsia conorii as a model organism. It highlights the current knowledge regarding the bacterial proteins and cognate host cell receptors involved in initiating this process. Early studies on the mechanism(s) utilized by rickettsiae to invade nonphagocytic mammalian cells identified cellular actin dynamics as playing an important role. In some invasive pathogens, depletion of membrane cholesterol using methyl-β-cyclodextrin disrupts the composition of lipid rafts and inhibits R.conorii invasion of nonphagocytic cells, suggesting that the presence of Ku70 within these microdomains is important for efficient bacterial entry. Mechanistic similarities to the invasion pathways utilized by zippering pathogens suggested that R.conorii also usurps these types of signaling events. Bioinformatic analyses of sequenced rickettsial genomes revealed the presence of a gene family. Four genes in this family, namely sca0, sca1, sca2, and sca5, are present as intact open reading frames in the genomes of the majority of SFGR. The signals involved in rickettsial outer membrane protein B (rompB)-dependent invasion closely resemble those observed during the invasion of R.conorii into Vero cells and include the activation of actin and microtubule dynamics and the stimulation of protein tyrosine kinase and PI-kinase activities.