Comparative Genomics of Emerging Human Ehrlichiosis Agents

Abstract

Anaplasma (formerly Ehrlichia) phagocytophilum, Ehrlichia chaffeensis, and Neorickettsia (formerly Ehrlichia) sennetsu are intracellular vector-borne pathogens that cause human ehrlichiosis, an emerging infectious disease. We present the complete genome sequences of these organisms along with comparisons to other organisms in the Rickettsiales order. Ehrlichia spp. and Anaplasma spp. display a unique large expansion of immunodominant outer membrane proteins facilitating antigenic variation. All Rickettsiales have a diminished ability to synthesize amino acids compared to their closest free-living relatives. Unlike members of the Rickettsiaceae family, these pathogenic Anaplasmataceae are capable of making all major vitamins, cofactors, and nucleotides, which could confer a beneficial role in the invertebrate vector or the vertebrate host. Further analysis identified proteins potentially involved in vacuole confinement of the Anaplasmataceae, a life cycle involving a hematophagous vector, vertebrate pathogenesis, human pathogenesis, and lack of transovarial transmission. These discoveries provide significant insights into the biology of these obligate intracellular pathogens.

Phyletic distribution and conservation of the bacterial transcription termination factor Rho

“…In the case of Ehrlichia and Anaplasma spp., synteny also supports chromosomal duplication/ inversion events (Fig. S1), which tend to be frequent for these species (Dunning Hotopp et al, 2006).…”

A Variable-Length PCR Target Protein of Ehrlichia chaffeensis Contains Major Species-Specific Antibody Epitopes in Acidic Serine-Rich Tandem Repeats

“…VLPT was predicted by SecretomeP 2.0 to be secreted by a nonclassical and leaderless secretion system; therefore, secretion of VLPT and other TR-containing proteins may occur by a similar mechanism to that for E. chaffeensis gp120 and gp47, which also lack an N-terminal signal sequence but are found outside the bacterium in the morula and in infected cell culture supernatants. Genes encoding type IV secretion system components have been reported for both Ehrlichia and Anaplasma (9,26), and AnkA of Anaplasma phagocytophilum appears to be secreted by this system (14). However, the VLPT does not appear to contain a type IV effector protein consensus sequence (R-X 7 -R-X-R-X-R-X-X n ) and could be a substrate of other secretion systems (sec dependent and sec independent) that have been identified in Ehrlichia species (9).…”

“…Genes encoding type IV secretion system components have been reported for both Ehrlichia and Anaplasma (9,26), and AnkA of Anaplasma phagocytophilum appears to be secreted by this system (14). However, the VLPT does not appear to contain a type IV effector protein consensus sequence (R-X 7 -R-X-R-X-R-X-X n ) and could be a substrate of other secretion systems (sec dependent and sec independent) that have been identified in Ehrlichia species (9).…”

Extensive genomic diversity of closely related Wolbachia strains

“…Phylogenetic analysis of concatenated protein sequences and the 16S rRNA places Wolbachia in a clade of obligate intracellular bacteria including the tickand trematode-vectored vertebrate pathogens from the genera Anaplasma, Ehrlichia and Neorickettsia, as well as the more distantly related, but better characterized, arthropod-associated Rickettsia spp. (Dumler et al, 2001;Dunning Hotopp et al, 2006b). Numerous phylogenetic analyses of Wolbachia have been undertaken, including single-locus and multi-locus approaches (Bordenstein et al, 2008;Casiraghi et al, 2005;Lo et al, 2002;O'Neill et al, 1992;Werren et al, 1995;Zhou et al, 1998).…”