The Genome of the Obligately Intracellular Bacterium Ehrlichia canis Reveals Themes of Complex Membrane Structure and Immune Evasion Strategies

Abstract

Ehrlichia canis, a small obligately intracellular, tick-transmitted, gram-negative, ␣-proteobacterium, is the primary etiologic agent of globally distributed canine monocytic ehrlichiosis. Complete genome sequencing revealed that the E. canis genome consists of a single circular chromosome of 1,315,030 bp predicted to encode 925 proteins, 40 stable RNA species, 17 putative pseudogenes, and a substantial proportion of noncoding sequence (27%). Interesting genome features include a large set of proteins with transmembrane helices and/or signal sequences and a unique serine-threonine bias associated with the potential for O glycosylation that was prominent in proteins associated with pathogen-host interactions. Furthermore, two paralogous protein families associated with immune evasion were identified, one of which contains poly(G-C) tracts, suggesting that they may play a role in phase variation and facilitation of persistent infections. Genes associated with pathogen-host interactions were identified, including a small group encoding proteins (n ‫؍‬ 12) with tandem repeats and another group encoding proteins with eukaryote-like ankyrin domains (n ‫؍‬ 7).Ehrlichia spp., ␣-proteobacteria that belong to the order Rickettsiales, cause diseases of veterinary importance and are also responsible for emerging life-threatening anthropozoonoses. E. canis is a small obligately intracellular, gram-negative, dimorphic bacterium transmitted by the brown dog tick, Rhipicephalus sanguineus, that resides as a microcolony within a membrane-lined intracellular vacuole (morula), primarily within monocytes and macrophages of mammalian hosts (20,26,58). E. canis is the primary etiologic agent of canine monocytic ehrlichiosis, has a complex life cycle involving ticks, and is maintained in nature by persistent infection of wild and domestic canids (25). E. canis was first described in 1935 in Algeria (16) Clinically, E. canis infections progress in three phases: the acute, the subclinical, and the chronic (59, 62). With adequate treatment, dogs typically recover from the acute infections, but untreated or inappropriately treated dogs may develop subclinical persistent infections and thus can become asymptomatic carriers of the organism for years (20,31). Dogs that do not eliminate the infection can develop a severe chronic form of the disease, where bone marrow failure with anemia leads to opportunistic infections, poor response to treatment, and death from massive hemorrhage.Recent molecular characterization of E. canis has identified a limited set of major immunoreactive proteins that include glycoproteins and a major outer membrane protein family containing 25 paralogous genes that could be differentially expressed in the tick and mammalian hosts, contributing to persistent infections of the natural hosts (42, 50). Within the group of known major immunoreactive proteins, three glycoproteins have been identified in E. canis (gp36, gp140, and gp200) with corresponding orthologs in the human pathogen, E. chaffeensis (18,43,47). These g...

Detecção de proteínas imunorreativas de Rickettsia sp. cepa Mata Atlântica

“…A membrana externa de uma bactéria é responsável pela ligação entre o microrganismo e o hospedeiro, desempenhando um papel essencial na adesão à célula e na evasão da resposta imune do hospedeiro (Mavromatis et al 2006). As proteínas bacterianas que intercedem essas interações entre as diferentes espécies de riquétsias são alvos da resposta imune do hospedeiro e têm grande relevância no diagnóstico diferencial entre as espécies de riquétsias (Tjalsma et al 2008).…”

Functional genomic analysis of an uncultured δ-proteobacterium in the sponge Cymbastela concentrica

“…AR act as mediators for a diverse range of protein-protein interactions and are found commonly in eukaryotic and viral proteins, but rarely in bacteria (Lux et al, 1990;Bork, 1993;Mosavi et al, 2004). Eukaryotic-like AR have been reported in obligate intracellular bacteria such as the a-proteobacteria Wolbachia pipientis (IturbeOrmaetxe et al, 2005) and Ehrlichia canis (Mavromatis et al, 2006), as well as in the g-proteobacteria Legionella pneumophila (Habyarimana et al, 2008) and Coxiella butnetii (Voth et al, 2009). The involvement of AR proteins in host-bacterial associations and survival of the bacteria inside other cells has been highlighted recently by a mutant study of L. pneumophila, which showed that lack of certain AR proteins cause a significant defect in intracelluar replication (Habyarimana et al, 2008).…”

Tyrosine-Phosphorylated Ehrlichia chaffeensis and Ehrlichia canis Tandem Repeat Orthologs Contain a Major Continuous Cross-Reactive Antibody Epitope in Lysine-Rich Repeats

“…Genes encoding TRPs, including Ecaj_0472 (TRP95), were identified in the genome sequence of E. canis and previously reported (16). Oligonucleotide primers for the amplification of the E. chaffeensis TRP75 and E. canis TRP95 gene fragments were designed manually, or by PrimerSelect (Lasergene v8.1; DNAStar, Madison, WI) according to the sequences in GenBank (accession numbers U49426 and NC_007354, respectively) and synthesized (Sigma-Genosys, Woodlands, TX) ( Table 1).…”