The rickettsial effector Sca4 has a conserved interaction with host clathrin and a tick cell specific role in infection

Abstract

Intracellular bacterial pathogens secrete effectors to manipulate the host cell environment, create a hospitable niche, and promote infection. While many effectors interact with specific host machinery to perform a single distinct function, some effectors are capable of interaction with multiple host proteins to carry out multiple functions. Rickettsia species are obligate intracellular bacteria that cause vector-borne diseases that constitute an ongoing public health threat. As Rickettsia spp. have small genomes, and thus a limited coding capacity, multifunctional effectors may be an efficient way to manipulate their host environment. However, relatively few secreted effectors have been characterized in the Rickettsia genus and even fewer have been identified as multifunctional effectors.

In this work, I demonstrate that the rickettsial secreted effector Sca4 interacts with the host endocytic factor clathrin heavy chain. As previous work showed that Sca4 interacts with the host protein vinculin in mammalian cells, this discovery of the Sca4-clathrin interaction makes Sca4 one of the first multifunctional effectors to be identified in a Rickettsia species. When investigating the potential role of the Sca4-clathrin interaction, I found that clathrin promotes the cell-to-cell spread of R. parkeri in mammalian cells by acting in the recipient cell. However, the Sca4-clathrin interaction was found to be dispensable for efficient cell-to-cell spread. I investigated the role of this interaction in the tick arthropod vector and found that the Sca4-clathrin interaction is necessary for the efficient proliferation of R. parkeri in tick cells. These findings show that knowledge of the complete roles of rickettsial secreted effectors in both arthropod vector and mammalian hosts is needed to fully understand rickettsial pathogenesis.