Abstract

Adult schistosomes live in the host's bloodstream where they import nutrients such as glucose across their body surface (the tegument). The parasite tegument is an unusual structure since it is enclosed not by the typical one but by two closely apposed lipid bilayers. Within the tegument two glucose importing proteins have been identified; these are schistosome glucose transporter (SGTP) 1 and 4. SGTP4 is present in the host interactive, apical tegumental membranes, while SGTP1 is found in the tegumental basal membrane (as well as in internal tissues). The SGTPs act by facilitated diffusion. To examine the importance of these proteins for the parasites, RNAi was employed to knock down expression of both SGTP genes in the schistosomula and adult worm life stages. Both qRT-PCR and western blotting analysis confirmed successful gene suppression. It was found that SGTP1 or SGTP4-suppressed parasites exhibit an impaired ability to import glucose compared to control worms. In addition, parasites with both SGTP1 and SGTP4 simultaneously suppressed showed a further reduction in capacity to import glucose compared to parasites with a single suppressed SGTP gene. Despite this debility, all suppressed parasites exhibited no phenotypic distinction compared to controls when cultured in rich medium. Following prolonged incubation in glucose-depleted medium however, significantly fewer SGTP-suppressed parasites survived. Finally, SGTP-suppressed parasites showed decreased viability in vivo following infection of experimental animals. These findings provide direct evidence for the importance of SGTP1 and SGTP4 for schistosomes in importing exogenous glucose and show that these proteins are important for normal parasite development in the mammalian host.

Highlights

  • Schistosoma mansoni is a parasitic platyhelminth that causes the chronic, often debilitating disease, schistosomiasis affecting several hundred million people globally

  • The Schistosoma mansoni genome contains four facilitated glucose transporter genes The availability of a nearly complete draft of the S. mansoni genome [10] permits a careful bioinformatic analysis for facilitated glucose transport protein genes and this identifies a total of four schistosome glucose transporter (SGTP) genes

  • Searches of dbEST reveal that ESTs exist for all four SGTP genes demonstrating that these genes are expressed in mammalian stage schistosomes

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Summary

Introduction

Schistosoma mansoni is a parasitic platyhelminth that causes the chronic, often debilitating disease, schistosomiasis affecting several hundred million people globally. Infection is initiated following skin penetration by larval parasites called cercariae which rapidly adapt to the intra-mammalian environment in a process called cercarial transformation. These transformed juvenile parasites are called schistosomula and they move from the epidermal tissues into the blood stream where they mature. The internal, basal membrane of the tegument consists of a normal (trilaminate) lipid bilayer containing many invaginations. This bilayer extends periodically beneath the underlying muscle to enclose areas called ‘‘cell bodies’’ (or cytons) which contain nuclei and protein synthetic machinery [1]

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