Complex and dynamic transcriptional changes allow the helminth Fasciola gigantica to adjust to its intermediate snail and definitive mammalian hosts

Abstract

Background The tropical liver fluke, Fasciola gigantica causes fasciolosis, an important disease of humans and livestock. We characterized dynamic transcriptional changes associated with the development of the parasite in its two hosts, the snail intermediate host and the mammalian definitive host. Results Differential gene transcription analysis revealed 7445 unigenes transcribed by all F. gigantica lifecycle stages, while the majority (n = 50,977) exhibited stage-specific expression. Miracidia that hatch from eggs are highly transcriptionally active, expressing a myriad of genes involved in pheromone activity and metallopeptidase activity, consistent with snail host finding and invasion. Clonal expansion of rediae within the snail correlates with increased expression of genes associated with transcription, translation and repair. All intra-snail stages (miracidia, rediae and cercariae) require abundant cathepsin L peptidases for migration and feeding and, as indicated by their annotation, express genes putatively involved in the manipulation of snail innate immune responses. Cercariae emerge from the snail, settle on vegetation and become encysted metacercariae that are infectious to mammals; these remain metabolically active, transcribing genes involved in regulation of metabolism, synthesis of nucleotides, pH and endopeptidase activity to assure their longevity and survival on pasture. Dramatic growth and development following infection of the mammalian host are associated with high gene transcription of cell motility pathways, and transport and catabolism pathways. The intra-mammalian stages temporally regulate key families of genes including the cathepsin L and B proteases and their trans-activating peptidases, the legumains, during intense feeding and migration through the intestine, liver and bile ducts. While 70% of the F. gigantica transcripts share homology with genes expressed by the temperate liver fluke Fasciola hepatica, gene expression profiles of the most abundantly expressed transcripts within the comparable lifecycle stages implies significant species-specific gene regulation. Conclusions Transcriptional profiling of the F. gigantica lifecycle identified key metabolic, growth and developmental processes the parasite undergoes as it encounters vastly different environments within two very different hosts. Comparative analysis with F. hepatica provides insight into the similarities and differences of these parasites that diverged > 20 million years ago, crucial for the future development of novel control strategies against both species.

Molecular signatures of the rediae, cercariae and adult stages in the complex life cycles of parasitic flatworms (Digenea: Psilostomatidae)

“…Nevertheless, we assume that our conclusions about differential gene expression and the absolute numbers of upregulated and downregulated genes are more reliable for P. simillimum than for S. pseudoglobulus. Interestingly, BUSCO analysis of the recently published transcriptome of F. gigantica [25] also detects an elevated number of duplicated proteins (53%) ( Fig. 2a).…”

“…Nevertheless, comparative transcriptomic analysis is indispensable for understanding the origin and evolution of digenean life cycles and could provide new insights for the treatment and prevention of human and animal diseases. Several transcriptomes of digeneans have been sequenced recently [22][23][24][25][26][27][28][29][30][31][32][33][34][35], but in the majority of these studies only adult worms were analyzed [22, 23, 27-31, 33, 35]. Just a few studies analyzed gene expression among different life stages [25,32,34] or compared expression dynamics between the same life stages in the different species [23][24][25][26]35].…”

“…Several transcriptomes of digeneans have been sequenced recently [ 22 – 35 ], but in the majority of these studies only adult worms were analyzed [ 22 , 23 , 27 – 31 , 33 , 35 ]. Just a few studies analyzed gene expression among different life stages [ 25 , 32 , 34 ] or compared expression dynamics between the same life stages in the different species [ 23 – 26 , 35 ].…”

Complementary transcriptomic and proteomic analyses reveal the cellular and molecular processes that drive growth and development of Fasciola hepatica in the host liver

“…To further elucidate the key biological processes and molecular functions critical for the liver migrating immature flukes, we carried out a comparative analysis with transcriptome data from the F. gigantica immature (liver-stage) flukes recovered from buffalo at 42- and 70-days post infection [ 20 ] (Fig. 2 ).…”

“…Comparative analysis with the F. gigantica immature flukes recovered at 42- and 70-days post infection was carried using the previously published transcriptome dataset [ 20 ] based on GO analysis and the most highly transcribed genes calculated as FPKM. Enrichment of GO terms within the F. hepatica and F. gigantica datasets was determined using hypergeometric tests in R.…”