Functional Analysis of an Orientia tsutsugamushi Ankyrin Effector Protein in a Model Eukaryote

Abstract

Orientia tsutsugamushi is an understudied, gram negative, obligate intracellular bacterium that is transmitted by mites within the genus Leptotrombidium. This bacterium has an epidemic area called the Tsutsugamushi Triangle that spreads roughly 13 million km2 and an estimated one billion people are at risk of contracting the bacterium. Commonly this bacterium causes a disease called Scrub Typhus. There are many strains which cause a wide range of virulence. These strains have protein domains that have been originally identified as Eukaryotic. This domain is called Ankyrin Repeating Domain (Anks). Attached to several of these Anks are another domain call F-boxes. These F-boxes are typically used in the process of attaching ubiquitin to a substrate for later degradation by the cell. O. tsutsugamushi actively secretes these proteins into their host cell, but little is known what pathway these Ankyrin proteins are using. Our focus for this study was attempting to identify pathways for a set of these Anks.