Poster abstracts
Poster number 50 submitted by Rory Chia-Ching Chien
Pathogenesis of Two Newly Discovered Virulence Factors of Ehrlichia japonica, A Model Bacterium for Studying Fatal Human Monocytic Ehrlichiosis
Rory C. Chien (Department of Veterinary Biosciences, College of Veterinary Medicine ), Mingqun Lin (Department of Veterinary Biosciences, College of Veterinary Medicine ), Yasuko Rikihisa (Department of Veterinary Biosciences, College of Veterinary Medicine )
Abstract:
Human monocytic ehrlichiosis (HME) is an emerging, tick-borne febrile illness that potentially causes life-threatening infections. The causative pathogen, Ehrlichia chaffeensis, is a unique, obligate intracellular bacterium that primarily targets monocytes and macrophages. The in vivo pathogenesis of severe or fatal HME is not completely understood. Our laboratory developed a fatal HME mouse model by culture isolating Ehrlichia japonica, a bacterium closely related to E. chaffeensis, which causes severe diseases and death in immunocompetent mice due to cytokine storm and toxic shock-like syndrome. By using Himar1 transposon random mutagenesis system, we recently identified two novel virulence factors of E. japonica (EHF_0962 and EHF_RS04100) in the mutants H59 and H43B, respectively. Although these virulence factors are dispensable in vitro for infecting macrophage (DH82), endothelial (RF/6A), and tick (ISE6) cell lines, the H59 and H43B mutants cannot rapidly replicate and spread systemically to kill immunocompetent mice. My hypothesis is that the mutants lost the ability to overcome in vivo innate immune responses such as the reactive oxygen species (ROS) and reactive nitrogen species (RNS) generated by phagocytes. To investigate the virulence loss of the mutants, we will establish a time-coursed infection in the mouse model and design specific experiments for testing host innate immune responses. Furthermore, we will generate rescue plasmids to restore the virulence gene in the mutants for the complementation assays. Successful completion of these aims will provide critical knowledge of treating and preventing severe HME.
Keywords: Ehrlichia chaffeensis , Human monocytic ehrlichiosis , Virulence factors