Systems Biology Studies of Adult Paragonimus Lung Flukes Facilitate the Identification of Immunodominant Parasite Antigens

McNulty, Samantha N.; Fischer, Peter; Townsend, R. Reid; Curtis, Kurt C.; Weil, Gary J.; Mitreva, Makedonka

doi:10.1371/journal.pntd.0003242

Cited by 25 publications

(34 citation statements)

References 62 publications

(66 reference statements)

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“…As previously described [59], RNA quality and yield were assessed, the purified RNA was poly(A) selected, reverse transcribed, paired-end cDNA libraries were generated, sequenced on the Illumina HiSeq 2000 platform and reads were analytically processed. Remaining, high-quality RNAseq reads (from one egg, two metacercariae and two adult biological replicates) were aligned to the genome assembly and constitutively expressed and differentially expressed genes were identified using standard protocols outlined in S1 Text.…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2017

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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.

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Section: Methodsmentioning

confidence: 99%

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

et al. 2017

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“…Raw reads were subjected to stringent quality control and contaminant filtering as previously described [ 16 ]. Briefly, reads were trimmed to remove low quality regions, and filtered based on read length, sequence complexity, and similarity to known or suspected contaminants, including ribosomal RNA [ 17 , 18 ], bacteria [ 19 ], Homo sapiens (GenBank version hs37) and Canis familiaris (GenBank version 3.1).…”

Section: Methodsmentioning

confidence: 99%

Conservation and diversification of the transcriptomes of adult Paragonimus westermani and P. skrjabini

McNulty

Rosa

et al. 2016

Parasites Vectors

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BackgroundParagonimiasis is an important and widespread neglected tropical disease. Fifteen Paragonimus species are human pathogens, but two of these, Paragonimus westermani and P. skrjabini, are responsible for the bulk of human disease. Despite their medical and economic significance, there is limited information on the gene content and expression of Paragonimus lung flukes.ResultsThe transcriptomes of adult P. westermani and P. skrjabini were studied with deep sequencing technology. Approximately 30 million reads per species were assembled into 21,586 and 25,825 unigenes for P. westermani and P. skrjabini, respectively. Many unigenes showed homology with sequences from other food-borne trematodes, but 1,217 high-confidence Paragonimus-specific unigenes were identified. Analyses indicated that both species have the potential for aerobic and anaerobic metabolism but not de novo fatty acid biosynthesis and that they may interact with host signaling pathways. Some 12,432 P. westermani and P. skrjabini unigenes showed a clear correspondence in bi-directional sequence similarity matches. The expression of shared unigenes was mostly well correlated, but differentially expressed unigenes were identified and shown to be enriched for functions related to proteolysis for P. westermani and microtubule based motility for P. skrjabini.ConclusionsThe assembled transcriptomes of P. westermani and P. skrjabini, inferred proteins, and extensive functional annotations generated for this project (including identified primary sequence similarities to various species, protein domains, biological pathways, predicted proteases, molecular mimics and secreted proteins, etc.) represent a valuable resource for hypothesis driven research on these medically and economically important species.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-016-1785-x) contains supplementary material, which is available to authorized users.

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“…Raw reads were submitted to the GenBank sequence read archive (SRA) under BioProject PRJNA167264 (Supplementary Table S1). Reads were processed for quality, complexity and contamination as previously described (McNulty et al, 2014), and were aligned to the genome assembly (Jex et al, 2011) using Tophat2 (version 2.0.8, default parameters (Kim et al, 2013)) and counted using HTSeq-Count (Anders et al, 2015). …”

Section: Methodsmentioning

confidence: 99%

Direct experimental manipulation of intestinal cells in Ascaris suum , with minor influences on the global transcriptome

Rosa

McNulty

Mitreva

et al. 2017

International Journal for Parasitology

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Ascaris suum provides a powerful model for studying parasitic nematodes, including individual tissues such as the intestine, an established target for anthelmintic treatments. Here, we add a valuable experimental component to our existing functional, proteomic, transcriptomic and phylogenomic studies of the Ascaris suum intestine, by developing a method to manipulate intestinal cell functions via direct delivery of experimental treatments (in this case, double-stranded (ds)RNA) to the apical intestinal membrane. We developed an intestinal perfusion method for direct, controlled delivery of dsRNA/heterogeneous small interfering (hsi) RNA into the intestinal lumen for experimentation. RNA-Seq (22 samples) was used to assess influences of the method on global intestinal gene expression. Successful mRNA-specific knockdown in intestinal cells of adult A. suum was accomplished with this new experimental method. Global transcriptional profiling confirmed that targeted transcripts were knocked down more significantly than any others, with only 12 (0.07% of all genes) or 238 (1.3%) off-target gene transcripts consistently differentially regulated by dsRNA treatment or the perfusion experimental design, respectively (after 24 h). The system supports controlled, effective delivery of treatments (dsRNA/hsiRNA) to the apical intestinal membrane with relatively minor off-target effects, and builds on our experimental model to dissect A. suum intestinal cell functions with broad relevance to parasitic nematodes.

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Systems Biology Studies of Adult Paragonimus Lung Flukes Facilitate the Identification of Immunodominant Parasite Antigens

Cited by 25 publications

References 62 publications

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

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

Conservation and diversification of the transcriptomes of adult Paragonimus westermani and P. skrjabini

Direct experimental manipulation of intestinal cells in Ascaris suum , with minor influences on the global transcriptome

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