Proteome analysis of members of the family Anaplasmataceae
EMSL Project ID
15898
Abstract
Human monocytic ehrlichiosis (HME) and human granulocytic ehrlichiosis (HGE) caused by Ehrlichia chaffeensis and Anaplasma phagocytophilum, respectively are potentially fatal emerging zoonoses. A. phagocytophilum and E. chaffeensis are rickettsiae that live only inside eukaryotic host cells, and are transmitted by ticks. Neorickettsia sennetsu causes human Sennetsu rickettsiosis and is transmitted by a trematode. No vaccines are available and only a broad spectrum antibiotic, doxycycline is the choice of drug for treatment of human ehrlichioses. The severity of the disease varies from subclinical infection to severe morbidity which requires hospitalization, or death. The mechanisms responsible for clinical disease, horizontal transmission from invertebrate vector to humans, and the development of protective immunity are poorly understood. The long-term goal of this proposal is to identify genes in this group of bacteria that are required for internalization and survival in eukaryotic host cells, transmission between invertebrate vectors and mammals, and causing potentially fatal illness. We determined and annotated the complete nucleotide sequences of genomes of the A. phagocytophilum, E. chaffeensis, and N. sennetsu (Manuscript in preparation). Approximately 40-50% of ORFs encode proteins of unknown function, most of which are unique to each bacterium. Our laboratory developed tick transmission animal models of A. phagocytophilum and E. chaffeensis. Using these models and cell culture systems, we demonstrated differential expression of a set of genes by A. phagocytophilum and E. chaffeensis in human leukocytes in cell culture, in ticks and in mammalian blood. The production of distinct proteins during their intracellular life cycle, in invertebrate and mammalian hosts, may form the basis of an effective therapeutic, chemoprevention, and/or vaccination strategy to target critical gene products in these defined-stage parasites. We propose, therefore, to analyze proteome profiles of these bacteria. The study will help to identify functions of these bacteria-specific unknown genes, as well as confirming and further characterizing genes of predicted functions. The proposed studies will yield numerous new avenues for focused, hypothesis-based investigations aimed at delineating the role (s) of specific proteins in the life cycles of these pathogens. The results may point to potential chemopreventive and/or vaccine candidates for prevention of human ehrlichioses. Project Details
Project type
Exploratory Research
Start Date
2005-08-02
End Date
2007-06-28
Status
Closed
Released Data Link
Team
Principal Investigator
Related Publications
Huang H, M. Lin, X Wang, T Kikuchi, HM Mottaz, AD Norbeck, and Y Rikihisa. 2008. "Proteomic Analysis of and Immune Responses to Ehrlichia chaffeensis Lipoproteins." Infection and Immunity 76(8):3405-3414. doi:10.1128/IAI.00056-08
Lin M., T Kikuchi, HM Brewer, AD Norbeck, and Y Rikihisa. 2011. "Global proteomic analysis of two tick-borne emerging zoonotic agents: Anaplasma phagocytophilum and Ehrlichia chaffeensis." PNNL-SA-77990, Pacific Northwest National Laboratory, Richland, WA. [Unpublished]