Cell polarity in the obligate intracellular pathogen Rickettsia parkeri

About This Grant

The order Rickettsiales comprises arthropod-associated, obligate intracellular bacteria that are constrained to grow within a eukaryotic host as a result of substantial genome reduction. Their obligate intracellular lifestyle imposes challenges in culturing, genetically manipulating, and imaging these species. As a result, our understanding of fundamental aspects of rickettsial cell biology is limited. The Rickettsiales include a growing number of important human pathogens, however, and a mechanistic understanding of growth and cellular organization would potentiate therapeutic strategies to control rickettsial disease. Within the Rickettsia genus, the Spotted Fever Group (SFG) includes tick-borne human pathogens that cause diseases ranging from mild to life-threatening. Among the SFG bacteria, Rickettsia parkeri causes a relatively mild disease and presents a tractable model for probing the cell biology of this group. Interestingly, despite its reduced genome and lack of obvious morphological polarity, R. parkeri and other Rickettsiales encode putative cell polarity factors, including the polar organizing protein PopZ. We hypothesize that R. parkeri and other Rickettsiales exploit cell polarity to promote their intracellular growth and interactions with a host and that PopZ is important for establishing cell polarity in this group. Here, we propose to identify the suite of polar proteins in R. parkeri and functionally characterize PopZ’s role in growth and host interactions. In Aim 1, we will leverage proximity labeling to comprehensively identify the polar protein repertoire in R. parkeri and will validate putative polar proteins. In Aim 2, will leverage a transposon mutant of popZ to characterize the function of PopZ in fundamental events during R. parkeri growth and interactions with a host cell. Completion of this project will provide foundational knowledge on the mechanisms and function of cell polarity in an important tick-borne, obligate intracellular pathogen that may aid in the design of new antibacterial therapeutic approaches.