Ehrlichia canis Jake

Courtesy of V.L. Popov and Tom Bednarek
Ehrlichia canis, a member of the order Rickettsiales, is tick-borne small obligate intracellular, gram-negative, dimorphic bacterium that resides as a microcolony within a membrane-lined intracellular vacuole (morula), primarily in monocytes and macrophages of mammalian hosts. Each morula may contain 100 or more ehrlichiae. Ultrastructurally, E. canis has two forms, termed reticulate and dense-cored cells, resembling morphologically similar reticulate and elementary body forms of chlamydiae. Ehrlichiae have relatively small genomes (~1.2 Mbp) and do not possess extrachromosomal plasmids. Members of the genus Ehrlichia include E. chaffeensis, E. canis, E ewingii, E. ruminantium, and E. muris, and phylogenetic analysis of 16s rDNA and groEL genes support the close genetic relatedness of E. canis and E. chaffeensis. The genus Ehrlichia is closely related to the genera of Anaplasma and Neorickettsia, whose members have a similar intracellular lifestyle.

Canine ehrlichiosis is a general term that originally described a tick-transmitted disease in dogs caused by E. canis. It is now known that canine ehrlichiosis can be caused by multiple etiologic agents (E. canis, E. chaffeensis, E. ewingii, A. phagocytophila, and A. platys) with different host cell tropisms including monocytes, granulocytes, and platelets. Canine ehrlichiosis was first described as early as 1935 in Algeria, but has a global distribution that includes the United States. E. canis was first recognized as a disease in dogs in the United States in 1962, but became better known following outbreaks in British military dogs in Singapore in 1963, and United States military dogs in Vietnam beginning in 1968, that resulted in approximately 200 deaths over a four year period. Serosurveys conducted in 35 states indicate that the overall prevalence rate of canine ehrlichiosis is approximately 1.5%, with southwestern states having the highest prevalence, 2-6%. Clinically, E. canis infections are characterized by acute, subclinical, and chronic stages of infection. In the acute stage of the disease, dogs may resolve the disease, but develop subclinical persistent infections, and thus, become asymptomatic carriers of the infection. A severe chronic form of the disease sometimes occurs, in which the response to antibiotic therapy is poor and dogs often die from massive hemorrhage, severe debilitation or secondary infection. Ehrlichiae have a complex life cycle involving a tick vector and a mammalian host and have developed strategies to establish persistent infections in the natural hosts to insure their survival and transmission in nature. E. canis is transmitted between dogs by the brown dog tick Rhipicephalus sanguineus and is maintained in nature by persistent infection of both wild and domestic dogs. Nymphal or larval ticks typically are infected with E. canis by feeding on a persistently infected dog, and maintain the infection transtadially as the tick molts from stage to stage. The mechanism of persistent ehrlichial infection has not yet been determined, but recent studies have identified important immunoreactive proteins and potential pathogenic mechanisms of ehrlichiae. Members of the genus Ehrlichia have a multigene family encoding homologous, but distinct, major surface proteins. A recently characterized multigene loci of E. canis has been identified, with 25 paralogous genes encoding 28 kDa proteins that may be differentially expressed in the tick and mammalian hosts resulting in immune avoidance and persistent infections of the natural host. Furthermore, two large molecular weight glycoproteins have been identified in E. canis (gp140 and gp200) and the corresponding orthologs in E. chaffeensis. These glycoproteins are among the first such proteins described in pathogenic bacteria, and appear to be important targets of the host immune response and elicit a strong antibody response. Although some important genes, including those encoding immunoreactive proteins (p28, p140, gp200 and dsb) and the 16S rRNA, nadA, and groE, have been identified and sequenced, there is a very limited knowledge of genes involved in pathogenesis. Considering the inherent difficulties related to in vitro cultivation and genetic manipulation of ehrlichiae, the complete genome sequence will dramatically advance research towards understanding pathogenesis and immunity, and promote vaccine development.

The significance of the genome sequences of E. canis.

  1. Pathogenesis. Ehrlichiae attach to a host cell receptor through an adhesin, enter the host cell through phagocytosis and prevent phagosomal fusion with the lysosome, multiply in the vacuole, and finally are released from the host cell to begin a new life cycle. None of virulence factors involved in these processes has been identified for E. canis.
  2. Vaccine development and immunity. Defining the virulence factors and immunoprotective antigens is necessary for vaccine development
  3. Prophylaxis. Design of improved therapeutic and preventive pharmaceuticals would be useful for surface glycoproteins (gp120 and gp200).
  4. Genetic manipulation. Genetic manipulation of the intracellular pathogens is not currently possible. Sequence data will aid in the identification of bacteriophages and transposons that may be used for genetic manipulation of E. chaffeensis.