Reversing the Resistance Phenotype of the Biomphalaria glabrata Snail Host Schistosoma mansoni Infection by Temperature Modulation

Abstract

Biomphalaria glabrata snails that display either resistant or susceptible phenotypes to the parasitic trematode, Schistosoma mansoni provide an invaluable resource towards elucidating the molecular basis of the snail-host/schistosome relationship. Previously, we showed that induction of stress genes either after heat-shock or parasite infection was a major feature distinguishing juvenile susceptible snails from their resistant counterparts. In order to examine this apparent association between heat stress and snail susceptibility, we investigated the effect of temperature modulation in the resistant snail stock, BS-90. Here, we show that, incubated for up to 4 hrs at 32°C prior to infection, these resistant snails became susceptible to infection, i.e. shedding cercariae at 5 weeks post exposure (PE) while unstressed resistant snails, as expected, remained resistant. This suggests that susceptibility to infection by this resistant snail phenotype is temperature-sensitive ( ts). Additionally, resistant snails treated with the Hsp 90 specific inhibitor, geldanamycin (GA) after heat stress, were no longer susceptible to infection, retaining their resistant phenotype. Consistently, susceptible snail phenotypes treated with 100 mM GA before parasite exposure also remained uninfected. These results provide direct evidence for the induction of stress genes (heat shock proteins; Hsp 70, Hsp 90 and the reverse transcriptase [RT] domain of the nimbus non-LTR retrotransposon) in B. glabrata susceptibility to S. mansoni infection and characterize the resistant BS-90 snails as a temperature-sensitive phenotype. This study of reversing snail susceptibility phenotypes to S. mansoni provides an opportunity to directly track molecular pathway(s) that underlie the B. glabrata snail's ability to either sustain or destroy the S. mansoni parasite.

Author Summary

Biomphalaria glabrata snails that are either resistant or susceptible to the parasite, Schistosoma mansoni, have been an invaluable resource in studies aimed at understanding the molecular basis of the snail/schistosome interaction. Schistosomes cause the chronic debilitating disease schistosomiasis. Thus, it is hoped that dissecting pathways that underlie the snail/schistosome relationship might translate into alternative control strategies that will include blocking transmission of the parasite at the snail-stage of its development. Induction of stress genes is a feature distinguishing early exposed juvenile susceptible NMRI snails from resistant BS-90 snail stocks. To further analyze this apparent involvement of stress induction and snail susceptibility, here we applied heat stress to the resistant BS-90 snail, enhancing induction of stress genes (Hsp 70, Hsp 90 and RT) prior to infection. Results showed these resistant snails became susceptible, indicating resistance as being a temperature sensitive phenotype in these snails. Stressed resistant snails treated with the Hsp 90 specific inhibitor, geldanamycin, prior to exposure, were, however, shown to maintain their refractory phenotype. Interestingly, inhibitor treated susceptible snails also became non-susceptible. Collectively, these data point to stress induction as an important early step in the ability of S. mansoni to infect juvenile B. glabrata snails.