Schistosome infectivity in the snail, Biomphalaria glabrata, is partially dependent on the expression of Grctm6, a Guadeloupe Resistance Complex protein.

Schistosomiasis is one of the most important neglected tropical diseases. Despite effective chemotherapeutic treatments, this disease continues to afflict hundreds of millions of people. Understanding the natural intermediate snail hosts of schistosome parasites is vital to the suppression of this disease. A recently identified genomic region in Caribbean Biomphalaria glabrata snails strongly influences their resistance to infection by Schistosoma mansoni. This region contains novel genes having structural similarity to known pathogen recognition proteins. Here we elaborate on the probable structure and role of one of these genes, grctm6. We characterised the expression of Grctm6 in a population of Caribbean snails, and performed a siRNA knockdown of Grctm6. We show that this protein is not only expressed in B. glabrata hemolymph, but that it also has a role in modulating the number of S. mansoni cercariae released by infected snails, making it a possible target for the biological control of schistosomiasis.

Hyperdiverse gene cluster in snail host conveys resistance to human schistosome parasites.

Schistosomiasis, a neglected global pandemic, may be curtailed by blocking transmission of the parasite via its intermediate hosts, aquatic snails. Elucidating the genetic basis of snail-schistosome interaction is a key to this strategy. Here we map a natural parasite-resistance polymorphism from a Caribbean population of the snail Biomphalaria glabrata. In independent experimental evolution lines, RAD genotyping shows that the same genomic region responds to selection for resistance to the parasite Schistosoma mansoni. A dominant allele in this region conveys an 8-fold decrease in the odds of infection. Fine-mapping and RNA-Seq characterization reveal a <1Mb region, the Guadeloupe Resistance Complex (GRC), with 15 coding genes. Seven genes are single-pass transmembrane proteins with putative immunological roles, most of which show strikingly high nonsynonymous divergence (5-10%) among alleles. High linkage disequilibrium among three intermediate-frequency (>25%) haplotypes across the GRC, a significantly non-neutral pattern, suggests that balancing selection maintains diversity at the GRC. Thus, the GRC resembles immune gene complexes seen in other taxa and is likely involved in parasite recognition. The GRC is a potential target for controlling transmission of schistosomiasis, including via genetic manipulation of snails.

Mitochondrial DNA variation of the dog hookworm Ancylostoma caninum in Brazilian populations.

The mitochondrial cytochrome oxidase I gene was partially sequenced for 164 Ancylostoma caninum individuals, originating from five different localities in Brazil, with the aim of describing the genetic diversity and genetic structure of Brazilian hookworm populations. Allelic and nucleotide diversity were moderate (overall h=0.88 and pi=0.016) and were similar among cities. There was moderate genetic differentiation among the populations sampled (approximately Phi(ST)=0.12) and a weak but nonsignificant correlation between geographical and genetic distance. This genetic structure was similar to that observed among populations of the human hookworm, Necator americanus, but distinct from that typically found in trichostrongylid nematode parasites of livestock. Thus, a pattern of different genetic structures among different groups of nematodes is emerging. We also observed a few individuals that had a highly divergent mtDNA sequence (almost 7% sequence divergence from the other sequences). These results in combination with data from other studies suggest that A. caninum populations worldwide consist of a mix of previously differentiated populations, or perhaps even cryptic species. This study contributes to the knowledge of genetic structure and diversity of hookworms, which in turn will be useful in developing methods for their control.