Comparative Analysis of Genome of Ehrlichia sp. HF, a Model Bacterium to Study Fatal Human Ehrlichiosis

Abstract

Background The genus Ehrlichia consists of tick-borne obligatory intracellular bacteria that can cause deadly diseases of medical and agricultural importance. Ehrlichia sp. HF, isolated from Ixodes ovatus ticks in Japan [also referred to as I. ovatus Ehrlichia (IOE) agent], causes acute fatal infection in laboratory mice that resembles acute fatal human monocytic ehrlichiosis caused by Ehrlichia chaffeensis. As there is no small laboratory animal model to study fatal human ehrlichiosis, Ehrlichia sp. HF provides a needed disease model. However, the inability to culture Ehrlichia sp. HF and the lack of genomic information have been a barrier to advance this animal model. In addition, Ehrlichia sp. HF has several designations in the literature as it lacks a taxonomically recognized name. Results We stably cultured Ehrlichia sp. HF in canine histiocytic leukemia DH82 cells from the HF strain-infected mice, and determined its complete genome sequence. Ehrlichia sp. HF has a single double-stranded circular chromosome of 1,148,904 bp, which encodes 866 proteins with a similar metabolic potential as E. chaffeensis. Ehrlichia sp. HF encodes homologs of all virulence factors identified in E. chaffeensis, including 23 paralogs of P28/OMP-1 family outer membrane proteins, type IV secretion system apparatus and effector proteins, two-component systems, ankyrin-repeat proteins, and tandem repeat proteins. Ehrlichia sp. HF is a novel species in the genus Ehrlichia, as demonstrated through whole genome comparisons with six representative Ehrlichia species, subspecies, and strains, using average nucleotide identity, digital DNA-DNA hybridization, and core genome alignment sequence identity. Conclusions The genome of Ehrlichia sp. HF encodes all known virulence factors found in E. chaffeensis, substantiating it as a model Ehrlichia species to study fatal human ehrlichiosis. Comparisons between Ehrlichia sp. HF and E. chaffeensis will enable identification of in vivo virulence factors that are related to host specificity, disease severity, and host inflammatory responses. We propose to name Ehrlichia sp. HF as Ehrlichia japonica sp. nov. (type strain HF), to denote the geographic region where this bacterium was initially isolated.

Characterization of “Candidatus Ehrlichia Pampeana” in Haemaphysalis juxtakochi Ticks and Gray Brocket Deer (Mazama gouazoubira) from Uruguay

“…E. pampeana" for humans is uncertain, our results highlight eco-epidemiological features that might be relevant to suggest this novel Ehrlichia as a putative human pathogen as follows: (i) "Ca. E. pampeana" is phylogenetically closely related to E. ewingii, a recognized zoonotic pathogen [7], (ii) although H. juxtakochi parasitizes cervids, it has been also recorded feeding on humans [16,17], and (iii) the role of cervids as reservoirs for pathogenic Ehrlichia species has been previously suggested in North America [9].…”

“…These bacteria are the agents of ehrlichiosis, a complex of life-threatening emerging zoonoses and diseases of worldwide veterinary concern [6]. The genus Ehrlichia currently consists of six validly published species, namely Ehrlichia canis, Ehrlichia chaffeensis, Ehrlichia ewingii, Ehrlichia minasensis, Ehrlichia muris, and Ehrlichia ruminantium [7]. For all these species, sequences of the complete chromosome are already available in genetic databases [3].…”

“…For all these species, sequences of the complete chromosome are already available in genetic databases [3]. Four species (E. chaffeensis, E. ewingii, E. canis, and E. muris) are known to infect humans and cause potentially severe to fatal ehrlichiosis [7]. Cervids (Cervidae) have been demonstrated to be reservoirs of human pathogenic Ehrlichiae, particularly E. chaffeensis, E. ewingii, and E. muris [8][9][10][11][12].…”

Protective Immunity and Immunopathology in Ehrlichiosis

“…Analyses of genome sequences of cultured IOE/E. japonica have indicated that this Ehrlichia species has a single double-stranded circular chromosome of 1,148,904 bp, which encodes 866 proteins with similar metabolic functions to those of E. chaffeensis [37]. IOE/E.…”

Ecological and evolutionary perspectives on tick-borne pathogen co-infections

“…Fourth, ticks are laboratory-tractable and a number of cell lines have been shown to be effective for studying interactions between tick-borne pathogens in vitro ( Bell-Sakyi et al, 2007 ; Moniuszko et al, 2014 ). Fifth, different state-of-the-art omics and high-throughput technologies can be applied to ticks and their pathogens to tease apart the mechanisms underlying changes in infection-related traits ( Ayllón et al, 2015 ; Bekebrede et al., 2020 ; Lin et al, 2021 ). The use of this system can expand our knowledge on the ability of co-infections to shape the evolutionary biology of vector-borne pathogens.…”