Abstract
BackgroundThe debilitating human disease schistosomiasis is caused by infection with schistosome parasites that maintain a complex lifecycle alternating between definitive (human) and intermediate (snail) hosts. While much is known about how the definitive host responds to schistosome infection, there is comparably less information available describing the snail’s response to infection.Methodology/Principle findingsHere, using information recently revealed by sequencing of the Biomphalaria glabrata intermediate host genome, we provide evidence that the predicted core snail DNA methylation machinery components are associated with both intra-species reproduction processes and inter-species interactions. Firstly, methyl-CpG binding domain protein (Bgmbd2/3) and DNA methyltransferase 1 (Bgdnmt1) genes are transcriptionally enriched in gonadal compared to somatic tissues with 5-azacytidine (5-AzaC) treatment significantly inhibiting oviposition. Secondly, elevated levels of 5-methyl cytosine (5mC), DNA methyltransferase activity and 5mC binding in pigmented hybrid- compared to inbred (NMRI)- B. glabrata populations indicate a role for the snail’s DNA methylation machinery in maintaining hybrid vigour or heterosis. Thirdly, locus-specific detection of 5mC by bisulfite (BS)-PCR revealed 5mC within an exonic region of a housekeeping protein-coding gene (Bg14-3-3), supporting previous in silico predictions and whole genome BS-Seq analysis of this species’ genome. Finally, we provide preliminary evidence for parasite-mediated host epigenetic reprogramming in the schistosome/snail system, as demonstrated by the increase in Bgdnmt1 and Bgmbd2/3 transcript abundance following Bge (B. glabrata embryonic cell line) exposure to parasite larval transformation products (LTP).Conclusions/SignificanceThe presence of a functional DNA methylation machinery in B. glabrata as well as the modulation of these gene products in response to schistosome products, suggests a vital role for DNA methylation during snail development/oviposition and parasite interactions. Further deciphering the role of this epigenetic process during Biomphalaria/Schistosoma co-evolutionary biology may reveal key factors associated with disease transmission and, moreover, enable the discovery of novel lifecycle intervention strategies.
Highlights
With over 200 million people at risk of infection and approximately 200,000 deaths per year, schistosomiasis is the second most significant human parasitic disease on the planet [1]
The transcript sequence encoding the 242 aa predicted ORF of the B. glabrata MBD2/3 (BgMBD2/ 3) homolog was subsequently amplified from adult NMRI head/foot cDNA and PFAM domain search analysis of the cloned product (GenBank: KJ951055) revealed the presence of a Nterminal MBD domain (PF01429), as well as a C-terminal domain conserved amongst proteins of the MBD2 and MBD3 family (PF14048)
Unlike the mammalian MBD3, which contains limited 5-methyl cytosine (5mC) binding capability due to a single amino acid substitution [60], the presence of crucial residues, essential for the binding of the protein to methylated DNA [32], enables us to propose that the snail homolog would be a functional member of this protein family
Summary
With over 200 million people at risk of infection and approximately 200,000 deaths per year, schistosomiasis is the second most significant human parasitic disease on the planet [1]. Three genera of pulmonate snails, Bulinus, Oncomelania and Biomphalaria, represent the most important intermediate hosts of medically important schistosome species (Schistosoma haematobium, Schistosoma japonicum and Schistosoma mansoni respectively). Anthropogenic activities, such as the construction of dams or development of irrigation schemes are commonly responsible for the population expansion of these snails [2,3] and, result in the spread of this neglected tropical disease into previously unaffected regions. While much is known about how the definitive host responds to schistosome infection, there is comparably less information available describing the snail’s response to infection
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