Introduction
Schistosomes are intravascular platyhelminths that infect approximately 200 million people globally as well as numerous domestic and wild animals (Skelly, Reference Skelly2008). Juvenile worms migrate to the portal blood vessels where they mate and then travel as couples to egg-laying sites. The adult worms are relatively large and highly mobile within the vasculature. The parasites have an unusual outer covering called the tegument. The tegument lacks lateral membranes and its cytoplasm extends as a continuous unit (a syncytium) around the entire body (Morris & Threadgold, Reference Morris and Threadgold1968; Smith et al., Reference Smith, Reynolds and Von Lichtenberg1969). The syncytium contains mitochondria and two kinds of inclusion bodies: discoid bodies (DBs) and multilaminate vesicles (MLVs) (Wilson & Barnes, Reference Wilson and Barnes1974b). DBs are ~40 × 200 nm in size, are surrounded by a single lipid bilayer and have a granular, mucopolysaccharide content (Wilson & Barnes, Reference Wilson and Barnes1974b). MLVs are 150–200 nm in diameter and appear as a mass of tightly packed concentrically arranged membranes. The tegumental cytoplasm is connected by numerous slender processes to cell bodies (cytons) that lie beneath the peripheral muscle layers. These contain one or more nuclei as well as Golgi complexes, endoplasmic reticulum and mitochondria (Morris & Threadgold, Reference Morris and Threadgold1968; Silk et al., Reference Silk, Spence and Gear1969). Proteins and carbohydrates for export are synthesized in the cytons and packaged into the secretory inclusions by Golgi bodies for transport along the cytoplasmic connections to the tegumental cytoplasm (Smith et al., Reference Smith, Reynolds and Von Lichtenberg1969).
The external tegument surface of schistosomes has a multilaminate, double lipid bilayer, appearance that can be seen using electron microscopy when uranyl acetate is used as a fixative in addition to the conventional glutaraldehyde and osmium tetroxide (Hockley & McLaren, Reference Hockley and McLaren1973). This unusual multilaminate feature is interpreted to comprise an inner, conventional plasma membrane that is covered by a membraneous secretion called the membranocalyx. It has been proposed that the tegumental multilaminate appearance arises when MLVs fuse with the inner plasma membrane and release their contents to form the overlying membranocalyx (Wilson & Barnes, Reference Wilson and Barnes1974a). The unusual tegumental outer covering is considered to be an adaptation for survival by schistosomes in the bloodstream. Internally the tegument is bounded by a basal membrane which is separated from the underlying musculature by a finely granular basal lamina or basement membrane (Silk et al., Reference Silk, Spence and Gear1969).
The tegument is a prime site of host–parasite interaction and there is great interest in understanding the composition and capabilities of the tegumental surface membranes. This is a long-term goal of our laboratory. The molecular composition of the outer surface membranes of intra-mammalian schistosomes has been the subject of much recent study. A series of investigations has used proteomics to characterize by direct analysis the composition of the host–parasite interface (Braschi & Wilson, Reference Braschi and Wilson2005; van Balkom et al., Reference van Balkom, van Gestel, Brouwers, Krijgsveld, Tielens, Heck and van Hellemond2005; Braschi et al., Reference Braschi, Curwen, Ashton, Verjovski-Almeida and Wilson2006). These studies have involved several different approaches. In some cases tegumental material was preferentially enriched and subjected to proteomic analyses (Braschi & Wilson, Reference Braschi and Wilson2005; van Balkom et al., Reference van Balkom, van Gestel, Brouwers, Krijgsveld, Tielens, Heck and van Hellemond2005; Braschi et al., Reference Braschi, Curwen, Ashton, Verjovski-Almeida and Wilson2006). In another case, the outer tegument was labelled with biotin and labelled protein was subsequently recovered and analysed by mass spectrometry (Braschi & Wilson, Reference Braschi and Wilson2005; van Balkom et al., Reference van Balkom, van Gestel, Brouwers, Krijgsveld, Tielens, Heck and van Hellemond2005; Braschi et al., Reference Braschi, Curwen, Ashton, Verjovski-Almeida and Wilson2006). More recently, exposed material has been removed enzymatically from whole worms using trypsin or phospholipase C and these ‘tegumental shavings’ analysed (Castro-Borges et al., Reference Castro-Borges, Dowle, Curwen, Thomas-Oates and Wilson2011a). Over 50 distinct, major proteins have been identified by these various approaches and these belong to a diversity of protein families, including enzymes, structural proteins and several others that are unique to schistosomes and of unknown function (Skelly & Wilson, Reference Skelly and Wilson2006). There is reasonable consistency between the different experimental approaches which have greatly expanded the number of known schistosome tegumental proteins. In some instances the newer proteomic analyses corroborate earlier reports defining proteins as being tegumental based on their immunolocalization patterns or activity profiles. In this report, we review work characterizing a number of tegumental components that are involved in transporting select metabolites across the tegument and describing how these proteins contribute to schistosome well-being.
Glucose transport
Despite the fact that schistosomes possess a mouth and a gut and are avid blood eaters, it has long been known that many nutrients are taken up by the parasites directly across the tegument (Fripp, Reference Fripp1967b; Asch & Read, Reference Asch and Read1975a, Reference Asch and Readb). Thus, one role of the intravascular parasite tegument is to import nutrients from the host bloodstream. Glucose is one metabolite that is copiously consumed; adult Schistosoma mansoni are reported to import across their teguments their dry weight in glucose every 5 h (Bueding, Reference Bueding1950) and at a rate three times higher than the glucose uptake by the mucosal border of the rabbit ileum (Gomme & Albrechtsen, Reference Gomme and Albrechtsen1988). Uptake is not an active process but is via facilitated diffusion (Isseroff et al., Reference Isseroff, Bonta and Levy1972; Uglem & Read, Reference Uglem and Read1975; Cornford et al., Reference Cornford, Fitzpatrick, Quirk, Diep and Landaw1988). These observations suggested that facilitated-diffusion glucose transporter proteins (GTPs) are localized within the schistosome tegument. We employed a degenerate polymerase chain reaction (PCR) approach to clone cDNAs encoding GTP homologues from S. mansoni (which we designated SGTP1 and SGTP4) (Skelly et al., Reference Skelly, Cunningham, Kim and Shoemaker1994). These proteins, both ~55 kDa, exhibited considerable sequence similarity with one another and with facilitated-diffusion glucose transporters of other organisms (Skelly & Shoemaker, Reference Skelly and Shoemaker1996; Zhao & Keating, Reference Zhao and Keating2007). In addition, they both contained structural features conserved in other characterized members of this sugar transporter family (Skelly et al., Reference Skelly, Cunningham, Kim and Shoemaker1994). Formal proof that SGTP1 and SGTP4 are sugar transporters was obtained by demonstrating expression of this property within Xenopus oocytes following their injection with RNA encoding SGTP1 or SGTP4. Both proteins functioned as typical facilitated-diffusion sugar transporters; they exhibited sodium independence, stereospecificity (transporting d-glucose but not l-glucose), relaxed specificity for other hexoses (also transporting mannose, maltose, galactose and fructose) and both were markedly blocked by the transport inhibitor cytochalasin B (Skelly et al., Reference Skelly, Cunningham, Kim and Shoemaker1994).
Both SGTP1 and SGTP4 were localized by immunofluorescence and immuno-electron microscopy to the tegument (Zhong et al., Reference Zhong, Skelly, Leaffer, Cohn, Caulfield and Shoemaker1995; Jiang et al., Reference Jiang, Skelly, Shoemaker and Caulfield1996; Skelly & Shoemaker, Reference Skelly and Shoemaker1996). SGTP4 was shown to be present in the host-interactive, apical tegumental membranes, while SGTP1 was found in the tegumental basal membrane. SGTP1 was also widely expressed in the internal tissues of the parasite. Because both SGTPs were functionally active following heterologous expression in Xenopus oocytes and both were found in the tegument, we hypothesized that SGTP4 (in the apical membranes) was required for glucose import into the tegument from the external environment and that SGTP1 (in the basal tegumental membrane and elsewhere) was required for the further movement of some of the imported glucose out of the tegument and into the internal tissues (Skelly et al., Reference Skelly, Tielens and Shoemaker1998).
The advent of RNA interference (RNAi) in schistosomes, permitting target gene suppression, provided us with the methodology to examine the importance of these proteins for the parasites and to test directly the hypothesis that these SGTPs were functional sugar importers in the worms. RNAi was employed to knock down expression of both SGTP genes in the schistosomula and adult worm life stages. In our laboratory we employ target gene specific, synthetic 27-mer short inhibitory RNAs (siRNAs) for RNAi, which we deliver to the parasites by electroporation (Ndegwa et al., Reference Ndegwa, Krautz-Peterson and Skelly2007; Bhardwaj et al., Reference Bhardwaj, Krautz-Peterson and Skelly2011). Gene suppression at the RNA level is routinely examined 2 days after treatment by quantitative real-time PCR (qRT-PCR). Suppression at the protein level is routinely monitored ~7 days after treatment by Western blotting. Both SGTP genes were effectively suppressed (either alone or in combination) as assessed at the RNA and protein levels (Krautz-Peterson et al., Reference Krautz-Peterson, Simoes, Faghiri, Ndegwa, Oliveira, Shoemaker and Skelly2010). Suppression is gene specific; when just SGTP1 is targeted, SGTP4 expression remains unaltered and vice versa. In glucose-uptake assays, SGTP1-suppressed or SGTP4-suppressed parasites exhibited an impaired ability to import radiolabelled sugar compared to control worms. This effect was compounded by suppression of both transporter genes simultaneously (Krautz-Peterson et al., Reference Krautz-Peterson, Simoes, Faghiri, Ndegwa, Oliveira, Shoemaker and Skelly2010). The reduced ability of SGTP-suppressed schistosomes to import glucose demonstrates unequivocally that the parasites do use both SGTP1 and SGTP4 to take in sugar efficiently. Not surprisingly, worms treated with the sugar transport inhibitor, cytochalasin B, are also greatly impaired in their ability to take up radiolabelled glucose (Krautz-Peterson et al., Reference Krautz-Peterson, Simoes, Faghiri, Ndegwa, Oliveira, Shoemaker and Skelly2010).
To determine if an inability to import glucose by the SGTP-suppressed parasites had a detrimental impact on the worms, their viability was compared with that of control parasites in vitro and in vivo. When suppressed parasites are maintained in standard culture medium with a high glucose concentration (10 mm) they exhibit no noticeable phenotypic differences compared with controls. However, when SGTP-suppressed parasites are cultured in medium containing a low glucose concentration (0.05 mm), significantly fewer of them survive relative to controls (Krautz-Peterson et al., Reference Krautz-Peterson, Simoes, Faghiri, Ndegwa, Oliveira, Shoemaker and Skelly2010). In the low-sugar environment, it appears that a diminished ability to import glucose impacts parasite metabolism and this leads to decreased worm viability. In a similar manner, when SGTP-suppressed parasites are used to infect mice, significantly fewer of them survive to maturation compared with controls (Krautz-Peterson et al., Reference Krautz-Peterson, Simoes, Faghiri, Ndegwa, Oliveira, Shoemaker and Skelly2010). This outcome shows that the SGTPs are essential for normal parasite development in the mammalian host.
Amino acid transport
In addition to importing glucose across the tegument, schistosomes have long been known to be capable of transporting amino acids from the external environment directly across their body surface (Fripp, Reference Fripp1967a; Asch & Read, Reference Asch and Read1975b). In early studies of amino acid transport into adult male schistosomes, at least five amino acid transport systems were implicated (Asch & Read, Reference Asch and Read1975a), indicative of the presence of several specific tegumental membrane amino acid transporter proteins. This is consistent with work in other cellular systems which employ multiple different amino acid transporter systems, some having a specialized role and others a more general role (Castagna et al., Reference Castagna, Shayakul, Trotti, Sacchi, Harvey and Hediger1997). So far, a single amino acid transporter has been characterized in schistosomes. This protein – designated schistosome permease 1 light chain, SPRM1lc – belongs to the glycoprotein-associated family of transporters (Mastroberardino et al., Reference Mastroberardino, Spindler, Pfeiffer, Skelly, Loffing, Shoemaker and Verrey1998; Skelly et al., Reference Skelly, Pfeiffer, Verrey and Shoemaker1999). SPRM1lc is a ~55 kDa protein that is found in both larval and adult schistosomes and in a variety of tissues (Skelly et al., Reference Skelly, Pfeiffer, Verrey and Shoemaker1999). When expressed in Xenopus oocytes, SPRM1lc promoted amino acid uptake but, in initial work, only when co-expressed with the human glycoprotein, h4F2hc (Mastroberardino et al., Reference Mastroberardino, Spindler, Pfeiffer, Skelly, Loffing, Shoemaker and Verrey1998). In this context, SPRM1lc facilitated the transport of the basic amino acids arginine, lysine and histidine as well as leucine, phenylalanine, methionine and glutamine (Mastroberardino et al., Reference Mastroberardino, Spindler, Pfeiffer, Skelly, Loffing, Shoemaker and Verrey1998; Skelly et al., Reference Skelly, Pfeiffer, Verrey and Shoemaker1999). The h4F2hc protein acted as a chaperone and was necessary for SPRM1lc to reach the oocyte plasma membrane and function as an amino acid permease. A disulphide bond links h4F2hc and SPRM1lc (Pfeiffer et al., Reference Pfeiffer, Spindler, Loffing, Skelly, Shoemaker and Verrey1998). In schistosome extracts of all life-cycle stages examined, SPRM1lc was found to be associated into a high molecular weight complex that could be disrupted by reducing agents (Skelly et al., Reference Skelly, Pfeiffer, Verrey and Shoemaker1999). We interpreted this to mean that a large fraction of endogenous SPRM1lc is linked via a disulphide bond to the schistosome h4F2hc homologue. Analysis of the schistosome genome led to the identification of a single h4F2hc homologue. We call this ~72 kDa protein the schistosome amino acid permease heavy chain or SPRM1hc (Krautz-Peterson et al., Reference Krautz-Peterson, Camargo, Huggel, Verrey, Shoemaker and Skelly2007). When SPRM1lc is co-expressed with SPRM1hc in Xenopus oocytes, the pattern of amino acid uptake detected is very similar to that reported for oocytes expressing SPRM1lc with h4F2hc (Krautz-Peterson et al., Reference Krautz-Peterson, Camargo, Huggel, Verrey, Shoemaker and Skelly2007), showing that heavy-chain influence is minor and that it is the light-chain partner that is most responsible for the uptake characteristics of the heterodimer.
Both SPRM1lc and SPRM1hc are detected in all life stages examined. This is consistent with their role in amino acid uptake into cells, an important function that would likely be required by all life stages and all tissues. Both proteins have been shown to be widely expressed in the adult parasites and both localize to the tegumental membranes. Localization of these proteins at the host/parasite interface has been confirmed for SPRM1lc, which has been shown to be available for surface biotinylation on living worms (Skelly et al., Reference Skelly, Pfeiffer, Verrey and Shoemaker1999; Braschi & Wilson, Reference Braschi and Wilson2005), and for SPRM1hc, which has been identified by proteomics in isolated tegumental membranes (Skelly et al., Reference Skelly, Pfeiffer, Verrey and Shoemaker1999; Braschi & Wilson, Reference Braschi and Wilson2005). These data strongly suggest that the SPRM1hc/SPRM1lc heterodimer functions not only to import amino acids from the external environment into the tegument but also to move amino acids from there into the internal tissues.
Water transport
Aquaporins are integral membrane proteins that act as water channels. Some aquaporins are capable of also transporting other small uncharged solutes, such as glycerol and urea, across a membrane and these are known more precisely as aquaglyceroporins (Gonen & Walz, Reference Gonen and Walz2006). Aquaporins/aquaglyceroporins are widespread in nature, where they occur as tetramers in plasma membranes. Proteomic analysis of the schistosome tegumental membranes revealed the presence of an aquaglyceroporin homologue at the host-interactive surface (Skelly et al., Reference Skelly, Pfeiffer, Verrey and Shoemaker1999; Braschi & Wilson, Reference Braschi and Wilson2005). The cDNA encoding the protein, which we designated SmAQP, was cloned and characterized (Faghiri & Skelly, Reference Faghiri and Skelly2009). It encodes a predicted ~33 kDa protein that is found largely in the schistosomula and adult parasite tegument, as determined by immunolocalization. SmAQP has highest relative expression in the intravascular life stages, as assessed by quantitative real-time PCR (Faghiri & Skelly, Reference Faghiri and Skelly2009). It is the most abundant constituent of adult schistosome tegumental membranes (Castro-Borges et al., Reference Castro-Borges, Simpson, Dowle, Curwen, Thomas-Oates, Beynon and Wilson2011b). To explore the function of SmAQP, parasites were treated with siRNAs targeting the SmAQP gene in order to silence its expression. This treatment results in potent (>90%) SmAQP gene suppression (Faghiri & Skelly, Reference Faghiri and Skelly2009). The suppressed parasites, lacking tegumental water channels, resist rapid swelling when placed in hypotonic medium, unlike their control counterparts which quickly double in volume (Faghiri & Skelly, Reference Faghiri and Skelly2009). Additionally, SmAQP-suppressed parasites, unlike controls, resist shrinkage when incubated in hyperosmotic solution (Faghiri & Skelly, Reference Faghiri and Skelly2009).
Formal demonstration of the ability of SmAQP to act as a water channel was seen following its expression in Xenopus oocytes. Oocytes expressing SmAQP rapidly swell and burst in less than 3 min when transferred from an isotonic to a hypotonic solution whereas non-injected oocytes survive at least until the end of the experiment (at 90 min). The water osmotic permeability (P f) in oocytes expressing SmAQP was 202 ± 36 × 10− 4 cm/s (Faghiri et al., Reference Faghiri, Camargo, Huggel, Forster, Ndegwa, Verrey and Skelly2010).
These experiments reveal a new function for the schistosome tegument – through SmAQP the tegument can act to control water movement into and out of the parasites and thus it plays a central role in parasite osmoregulation. The vital importance of SmAQP function is clear because the suppressed parasites exhibit lower viability in culture relative to controls and those that survive the RNAi treatment generally exhibit a stunted appearance following prolonged suppression (Faghiri & Skelly, Reference Faghiri and Skelly2009).
As noted earlier, aquaglyceroporins can act as conduits for substrates other than water. For instance, some aquaporins have been shown to play a role in controlling the exchange of metalloids (like arsenic and antimony) between an organism and its environment (Sanders et al., Reference Sanders, Rensing, Kuroda, Mitra and Rosen1997; Liu, Reference Liu2010). Some such metalloids have been used therapeutically and, until relatively recently, an important treatment option for schistosome infection involved the use of trivalent antimonials such as potassium antimony tartrate (Rodriguez-Molina et al., Reference Rodriguez-Molina, Acevedo, Torres, Lopez-Sanabria and Ramirez-Rodriguez1950; Bueding & Mansour, Reference Bueding and Mansour1957). In the case of the protozoan parasite leishmania, trivalent antimonials that kill the parasites enter through surface aquaporin proteins, and mutations in aquaporin genes confer resistance to the drugs (Gourbal et al., Reference Gourbal, Sonuc, Bhattacharjee, Legare, Sundar, Ouellette, Rosen and Mukhopadhyay2004). To test the hypothesis that, likewise in schistosomes, parasite-killing antimonial drugs enter through tegumental SmAQP, we compared the ability of potassium antimony tartrate to debilitate control versus SmAQP-suppressed parasites. The expectation was that parasites with reduced levels of SmAQP following RNAi treatment should have an impaired ability to take up the drug and should therefore exhibit a greater resistance to potassium antimony tartrate-mediated killing. Our data support this hypothesis; significantly fewer SmAQP-suppressed parasites were killed following exposure to potassium antimony tartrate compared to controls (Faghiri & Skelly, Reference Faghiri and Skelly2009). This result provides evidence that SmAQP can act as a conduit for anti-schistosome, antimonial drugs.
Lactate transport
The analysis of SmAQP function explored using RNAi reviewed above focused on the schistosomula life stage. In our analysis of SmAQP function in the adult life stage, we found that robust suppression of SmAQP (unlike the outcome in schistosomula) did not result in any detectable change in adult parasite viability or morphology (Faghiri et al., Reference Faghiri, Camargo, Huggel, Forster, Ndegwa, Verrey and Skelly2010). However, by serendipity we discovered that cultured adult parasites whose SmAQP expression is suppressed by RNAi treatment, unlike controls, fail to rapidly acidify their culture medium. We noted minimal colour change in the RPMI medium after 96 h in culture. The medium that contained SmAQP-suppressed adult worms looked redder (i.e. retained more phenol red indicator) than medium containing control worms. Direct measurement of the pH of the media confirmed that medium containing control worms was significantly more acidic than medium that contained the SmAQP-suppressed group (Faghiri et al., Reference Faghiri, Camargo, Huggel, Forster, Ndegwa, Verrey and Skelly2010). A key reason cultured schistosomes rapidly acidify their medium is because they excrete considerable amounts of lactic acid. The lactic acid is generated by the parasites largely following glucose catabolism through glycolysis. Adult schistosomes have long been termed homolactate fermenters because of their central reliance on glycolysis for energy generation (Shapiro & Talalay, Reference Shapiro and Talalay1982; Thompson et al., Reference Thompson, Morrison, Pax and Bennett1984). The large amount of glucose consumed by adult worms, mentioned earlier, is coupled to the generation of large amounts of lactic acid – the end product of glycolysis. Our observations of the SmAQP-suppressed parasites led to the hypothesis that they were impaired in their capacity to excrete lactic acid. To test this idea, the level of lactate in parasite culture medium was measured and, as predicted, medium from the SmAQP-suppressed group was found to contain significantly less lactate compared to media from control parasites (Faghiri et al., Reference Faghiri, Camargo, Huggel, Forster, Ndegwa, Verrey and Skelly2010). To directly test the hypothesis that SmAQP can transport lactate, the protein was expressed in Xenopus oocytes and radiolabelled lactate uptake assays were performed. It was found that SmAQP-expressing oocytes imported significantly more lactate versus controls (Faghiri et al., Reference Faghiri, Camargo, Huggel, Forster, Ndegwa, Verrey and Skelly2010). These data unequivocally demonstrated the ability of SmAQP to transport this substrate. The transport of lactate in SmAQP-expressing oocytes follows Michaelis–Menten kinetics with very low apparent affinity (K m = 41 ± 5. 8 mm) (Faghiri et al., Reference Faghiri, Camargo, Huggel, Forster, Ndegwa, Verrey and Skelly2010). Thus SmAQP functions not only to control water movement but also the movement of the metabolic by-product, lactate. The presence of SmAQP in the tegument of the worms assures an efficient efflux of lactate from the animals to the host-medium. Worms in culture can excrete 0.5 mmol/h of lactate in the medium and they can also accumulate a high concentration of lactate (Githui et al., Reference Githui, Damian and Aman2006a, Reference Asch and Readb). It is noteworthy that the low affinity of SmAQP for lactate is similar to that of the rat lactate transporter MCT4, expressed in Xenopus oocytes (Dimmer et al., Reference Dimmer, Friedrich, Lang, Deitmer and Broer2000). The MCT4 protein is reported to be adapted to the export of lactate from highly glycolytic cells (Dimmer et al., Reference Dimmer, Friedrich, Lang, Deitmer and Broer2000) and, as mentioned, adult schistosomes are also highly glycolytic. The transport of lactate (or water) into SmAQP-expressing Xenopus oocytes can be completely inhibited by the drug phloretin. Phloretin was previously shown to inhibit lactate release from cultured adult worms, presumably by acting on tegumental SmAQP (Githui et al., Reference Githui, Damian and Aman2006b).
Using the Xenopus oocyte uptake assay system, it was found that SmAQP can also transport mannitol and fructose but not glucose (Faghiri et al., Reference Faghiri, Camargo, Huggel, Forster, Ndegwa, Verrey and Skelly2010). Thus it appears that SmAQP is a versatile tegumental transporter controlling the movement of water, lactate and other metabolites across the parasite tegument.
Proteomic analysis of tegument fractions reveals that the tegument is likely involved in the transport of additional metabolites. For instance, ion transporters with associated ATPases can be found in tegumental membrane extracts (Skelly & Wilson, Reference Skelly and Wilson2006). Whether lipid is taken up trans-tegumentally is not known. Low-density lipoprotein (LDL) has been reported to bind to schistosomula and adult males of S. mansoni (Chiang & Caulfield, Reference Chiang and Caulfield1989; Pereira et al., Reference Pereira, Padilha, Lima-Filho and Chaves2011). However, endocytosis of LDL has not been reported. Further, no clear homologue of known lipid-binding proteins has been described in tegumental proteomic analyses (Skelly & Wilson, Reference Skelly and Wilson2006). Therefore additional work is needed to clarify how the worms acquire lipid, as well as to fully define other transport capabilities of the unique, intravascular schistosome surface.
Summary
In summary, this work shows that the intravascular schistosome tegument contains several transmembrane proteins that form channels or transporters necessary for parasite survival. Tegumental glucose transporters (SGTP1 and SGTP4) act to import sugar, the permease SPRM1lc (with the assistance of its heavy-chain chaperone SPRM1hc) acts to import some amino acids, and the aquaglyceroporin SmAQP can transport several metabolites (mannitol, fructose) including the metabolic waste product lactate. Impeding these important transport processes by targeting these proteins using chemotherapy or immunotherapy should offer new approaches to controlling schistosome infection.
