title: 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.
authors.affiliation: McDonnell Genome Institute at Washington University, St. Louis, Missouri, United States of America.
authors.forename: Samantha N
authors.initials: SN
authors.lastname: McNulty
authors.affiliation: Departamento de Genética, Facultad de Medicina, Universidad de la República (UDELAR), Montevideo, Uruguay.
authors.forename: Jose F
authors.identifier: 0000-0003-3950-9982
authors.initials: JF
authors.lastname: Tort
authors.affiliation: Department of Microbiology, Immunology and Tropical Medicine, and Research Center for Neglected Diseases of Poverty, School of Medicine & Health Sciences, George Washington University, Washington, DC, United States of America.
authors.forename: Gabriel
authors.identifier: 0000-0002-7767-4922
authors.initials: G
authors.lastname: Rinaldi
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: Kerstin
authors.identifier: 0000-0002-2963-1303
authors.initials: K
authors.lastname: Fischer
authors.affiliation: McDonnell Genome Institute at Washington University, St. Louis, Missouri, United States of America.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Rosa
authors.affiliation: Departamento de Genética, Facultad de Medicina, Universidad de la República (UDELAR), Montevideo, Uruguay.
authors.forename: Pablo
authors.identifier: 0000-0002-3856-3920
authors.initials: P
authors.lastname: Smircich
authors.affiliation: Departamento de Genética, Facultad de Medicina, Universidad de la República (UDELAR), Montevideo, Uruguay.
authors.forename: Santiago
authors.initials: S
authors.lastname: Fontenla
authors.affiliation: McDonnell Genome Institute at Washington University, St. Louis, Missouri, United States of America.
authors.forename: Young-Jun
authors.initials: YJ
authors.lastname: Choi
authors.affiliation: McDonnell Genome Institute at Washington University, St. Louis, Missouri, United States of America.
authors.forename: Rahul
authors.identifier: 0000-0002-6680-8972
authors.initials: R
authors.lastname: Tyagi
authors.affiliation: McDonnell Genome Institute at Washington University, St. Louis, Missouri, United States of America.
authors.forename: Kymberlie
authors.initials: K
authors.lastname: Hallsworth-Pepin
authors.affiliation: Department of Microbiology, Immunology and Tropical Medicine, and Research Center for Neglected Diseases of Poverty, School of Medicine & Health Sciences, George Washington University, Washington, DC, United States of America.
authors.forename: Victoria H
authors.identifier: 0000-0002-2218-597X
authors.initials: VH
authors.lastname: Mann
authors.affiliation: Department of Pathology, School of Medicine & Health Sciences, George Washington University, Washington, DC, United States of America.
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Kammili
authors.affiliation: Department of Pathology, School of Medicine & Health Sciences, George Washington University, Washington, DC, United States of America.
authors.forename: Patricia S
authors.initials: PS
authors.lastname: Latham
authors.affiliation: Departamento de Genética, Facultad de Medicina, Universidad de la República (UDELAR), Montevideo, Uruguay.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Dell'Oca
authors.affiliation: Departamento de Genética, Facultad de Medicina, Universidad de la República (UDELAR), Montevideo, Uruguay.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Dominguez
authors.affiliation: Unidad de Biología Parasitaria, Instituto de Biología, Facultad de Ciencias, Instituto de Higiene, Montevideo, Uruguay.
authors.forename: Carlos
authors.initials: C
authors.lastname: Carmona
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: Peter U
authors.initials: PU
authors.lastname: Fischer
authors.affiliation: Department of Microbiology, Immunology and Tropical Medicine, and Research Center for Neglected Diseases of Poverty, School of Medicine & Health Sciences, George Washington University, Washington, DC, United States of America.
authors.forename: Paul J
authors.identifier: 0000-0003-1765-0002
authors.initials: PJ
authors.lastname: Brindley
authors.affiliation: McDonnell Genome Institute at Washington University, St. Louis, Missouri, United States of America.|Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: Makedonka
authors.initials: M
authors.lastname: Mitreva
mesh_terms: D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics; D016873:Ehrlichiosis / Q000382:microbiology / Q000635:transmission / Q000662:veterinary; D005210:Fasciola hepatica / Q000235:genetics* / Q000302:isolation & purification / Q000382:microbiology; D016680:Genome, Bacterial; D049751:Genome, Helminth; D006734:Horse Diseases / Q000382:microbiology / Q000635:transmission; D006736:Horses; D006801:Humans; D041101:Neorickettsia sennetsu / Q000235:genetics* / Q000472:pathogenicity; D009922:Oregon; D012756:Sheep / Q000469:parasitology; D014583:Uruguay
chemical_list: D001425:Bacterial Outer Membrane Proteins