Illnesses caused by rickettsiales of the genera Ehrlichia and Anaplasma are a growing human health concern in recent years and are the second leading cause of tick-borne infections in the USA and many parts of the world. They include human monocytic ehrlichiosis caused by Ehrlichia chaffeensis. Despite the sophisticated systems of defense in vertebrate and tick hosts, the rickettsiales evade the host clearance. E. chaffeensis in macrophages and tick cells differ significantly in expression of several outer membrane proteins and effector proteins secreted via its secretary pathways. Research results demonstrate that differential tick and vertebrate host cell-specific expression contributes to the varied host response and delayed clearance in a host. The central hypothesis of the previously funded project is that E. chaffeensis differentially regulates gene expression and that the host-specific gene expression is essential for its survival in vertebrate and tick cells. Progress from the previous funding cycle forms the strong foundation for this renewal application and to continue testing the above stated innovative hypothesis.
Specific aims of this application are 1) to characterize E. chaffeensis RNA polymerase complex in support of understanding how vector and vertebrate host-specific differential gene expression is accomplished, 2) to evaluate the significance of host-specific differential expression by characterizing mutations in three genes identified as essential for E. chaffeensis in vivo growth, and 3) to perform mutational analysis and in vivo screening to identify genes essential for the E. chaffeensis pathogenesis.
The results from this study will provide important information for understanding E. chaffeensis pathogenesis, gene regulation and how the rickettsiale in vertebrate and tick hosts respond to the loss of expression from differentially expressed genes. This study will also allow us to determine how the tick transmitted pathogen persists and will aid in identifying targets for controlling E. chaffeensis infections.
|Raghavan, Ram K; Goodin, Douglas G; Hanzlicek, Gregg A et al. (2016) Maximum Entropy-Based Ecological Niche Model and Bio-Climatic Determinants of Lone Star Tick (Amblyomma americanum) Niche. Vector Borne Zoonotic Dis 16:205-11|
|Jaworski, Deborah C; Cheng, Chuanmin; Nair, Arathy D S et al. (2016) Amblyomma americanum ticks infected with in vitro cultured wild-type and mutants of Ehrlichia chaffeensis are competent to produce infection in naÃ¯ve deer and dogs. Ticks Tick Borne Dis :|
|Nair, Arathy D S; Cheng, Chuanmin; Ganta, Chanran K et al. (2016) Comparative Experimental Infection Study in Dogs with Ehrlichia canis, E. chaffeensis, Anaplasma platys and A. phagocytophilum. PLoS One 11:e0148239|
|McGill, Jodi L; Nair, Arathy D S; Cheng, Chuanmin et al. (2016) Vaccination with an Attenuated Mutant of Ehrlichia chaffeensis Induces Pathogen-Specific CD4+ T Cell Immunity and Protection from Tick-Transmitted Wild-Type Challenge in the Canine Host. PLoS One 11:e0148229|
|Raghavan, Ram K; Goodin, Douglas G; Neises, Daniel et al. (2016) Hierarchical Bayesian Spatio-Temporal Analysis of Climatic and Socio-Economic Determinants of Rocky Mountain Spotted Fever. PLoS One 11:e0150180|
|Nair, Arathy D S; Cheng, Chuanmin; Jaworski, Deborah C et al. (2015) Attenuated Mutants of Ehrlichia chaffeensis Induce Protection against Wild-Type Infection Challenge in the Reservoir Host and in an Incidental Host. Infect Immun 83:2827-35|
|Paddock, Christopher D; Denison, Amy M; Dryden, Michael W et al. (2015) High prevalence of "Candidatus Rickettsia andeanae" and apparent exclusion of Rickettsia parkeri in adult Amblyomma maculatum (Acari: Ixodidae) from Kansas and Oklahoma. Ticks Tick Borne Dis 6:297-302|
|Cheng, Chuanmin; Nair, Arathy D S; Jaworski, Deborah C et al. (2015) Mutations in Ehrlichia chaffeensis Causing Polar Effects in Gene Expression and Differential Host Specificities. PLoS One 10:e0132657|
|Raghavan, Ram K; Neises, Daniel; Goodin, Douglas G et al. (2014) Bayesian spatio-temporal analysis and geospatial risk factors of human monocytic ehrlichiosis. PLoS One 9:e100850|
|Stoffel, Ryan T; McClure, Jennifer C; Butcher, Marion M et al. (2014) Experimental infection of Rhipicephalus sanguineus with Ehrlichia chaffeensis. Vet Microbiol 172:334-8|
Showing the most recent 10 out of 26 publications