Arthropod and vertebrate determinants for horizontal transmission of Rickettsia felis

Rickettsia felis is a gram-negative bacterium predominantly described in the cat flea, Ctenocephalides felis. Since first described in 1990 in a commercial cat flea colony in the United States, R. felis has been detected in numerous arthropod species in 28 countries around the world. Additionally, as the etiologic agent of flea-borne rickettsiosis, R. felis can cause disease in humans, with patients presenting with clinical symptoms typical of rickettsial diseases including: fever, headache, and myalgia. Transmission of R. felis within flea colonies is predominantly via vertical (transovarial and transstadial) transmission and mechanisms of horizontal transmission are undescribed. Studies are needed to describe both arthropod and vertebrate determinants of R. felis horizontal transmission. Here we describe the development of both arthropod and vertebrate models of R. felis infection and use the tools of molecular biology to characterize R. felis infection in both models. We first characterized R. felis-infection in a naturally R. felis-infected cat flea colony and observed that the prevalence of R. felis-infection within a cat flea colony is dynamic with an inverse relationship between R. felis-infection density and prevalence of R. felis-infection in the colony. Also, over the flea lifespan, R. felis infection remains steady with little fluctuation during the onset of flea bloodmeal acquisition and oogenesis. After characterizing R. felis replication in naturally infected fleas, we developed a biological assay to infect naïve fleas. This is the first demonstration of oral acquisition and persistent R. felis-infection of fleas fed an R. felis-infected bloodmeal. Lastly, we describe the initial results of a murine model of R. felis infection. In this model, R. felis efficiently disseminated in the mouse and is detectable in several tissues including the spleen and liver for up to 14-days post-inoculation. Elucidation of both arthropod and vertebrate determinant for R. felis transmission is necessary to understand the ecology of R. felis in nature