Genomes of Fasciola hepatica from the Americas Reveal Colonization with Neorickettsia Endobacteria Related to the Agents of Potomac Horse and Human Sennetsu Fevers

Abstract

Food borne trematodes (FBTs) are an assemblage of platyhelminth parasites transmitted through the food chain, four of which are recognized as neglected tropical diseases (NTDs). Fascioliasis stands out among the other NTDs due to its broad and significant impact on both human and animal health, as Fasciola sp., are also considered major pathogens of domesticated ruminants. Here we present a reference genome sequence of the common liver fluke, Fasciola hepatica isolated from sheep, complementing previously reported isolate from cattle. A total of 14,642 genes were predicted from the 1.14 GB genome of the liver fluke. Comparative genomics indicated that F. hepatica Oregon and related food-borne trematodes are metabolically less constrained than schistosomes and cestodes, taking advantage of the richer millieux offered by the hepatobiliary organs. Protease families differentially expanded between diverse trematodes may facilitate migration and survival within the heterogeneous environments and niches within the mammalian host. Surprisingly, the sequencing of Oregon and Uruguay F. hepatica isolates led to the first discovery of an endobacteria in this species. Two contigs from the F. hepatica Oregon assembly were joined to complete the 859,205 bp genome of a novel Neorickettsia endobacterium (nFh) closely related to the etiological agents of human Sennetsu and Potomac horse fevers. Immunohistochemical studies targeting a Neorickettsia surface protein found nFh in specific organs and tissues of the adult trematode including the female reproductive tract, eggs, the Mehlis’ gland, seminal vesicle, and oral suckers, suggesting putative routes for fluke-to-fluke and fluke-to-host transmission. The genomes of F. hepatica and nFh will serve as a resource for further exploration of the biology of F. hepatica, and specifically its newly discovered trans-kingdom interaction with nFh and the impact of both species on disease in ruminants and humans.

Profiling G protein-coupled receptors of Fasciola hepatica identifies orphan rhodopsins unique to phylum Platyhelminthes

“…We exploited two F. hepatica genome assemblies available from WormBase ParaSite [83], generated by Liverpool University (http://parasite.wormbase.org/Fasciola_hepatica_prjeb6687/Info/Index/; [18], and Washington University, St Louis (http://parasite.wormbase.org/Fasciola_hepatica_prjna179522/Info/Index/; [19].…”

“…Despite two F. hepatica genomes [18,19], no GPCR sequences have been reported from F. hepatica. In contrast, GPCRs have been profiled in the genomes of trematodes ( Schistosoma mansoni and Schistosoma haematobium [20,21]), cestodes ( Echinococcus multilocularis, E. granulosus, Taenia solium and Hymenolepis microstoma [22]), and planaria ( Schmidtea mediterranea, Girardia tigrina [21–24]).…”

A Multi-Omics Database for Parasitic Nematodes and Trematodes

“…Our recent focus has been to provide tracks for SNPs and SNP annotations in the browser. At present there are genetic variants called from 27 strains of the river blindness agent Onchocerca volvulus [24], nine strains for the lungworm Dictyocaulus viviparus [25], a susceptible and a resistant strain of Trichostongylus circumcincta (unpublished) and 7 strains of Fasciola hepatica [26]. …”

Draft genome of the liver fluke Fasciola gigantica

“…Total of 46 GO terms were assigned and 4 genes had missing GO terms (Supplementary Table S2). The proteins which were significantly enriched are classified in the following GO terms, proteolysis, cysteine-type endopeptidase activity and regulation of catalytic activity 29 . The GO terms of ES proteins were classified in 0 CC, 19 MP and 13 BP.…”

“…Recently genomes from the parasitic flukes including Schistosoma japonicum 21 , S. mansoni 22 , S. haematobium 23,24 , Opisthorchis viverrni 25 , Clonorchis sinensis 26,27 and F. hepatica 28,29 have been sequenced. The genome sequences shed light on how these organisms survive in the host environment and show that the metabolic pathways in the parasite are highly adapted to the host conditions.…”