A molecular genetic study of the variations in metabolic function during schistosome development

Abstract

During their complex life cycle schistosomes alternate between the use of stored glycogen and reliance on host glucose to provide for their energy needs. In addition, there is dramatic variation between the relative contribution of aerobic versus anaerobic glucose metabolism during development. We have cloned a set of representative cDNAs that encode proteins involved in glucose uptake, glycolysis, Kreb's cycle and oxidative phosphorylation. The different cDNAs were used as probes to examine the expression of glucose metabolism genes during the schistosome life cycle. Steady state mRNA levels from whole cercariae, isolated cercarial tails, schistosomula and adult worms were analysed on Northern blots and dot blots which were quantified using storage phosphor technology. These studies reveal: (1) Transcripts encoding glycogen metabolic enzymes are expressed to much higher levels in cercarial tails than whole cercariae or schistosomula while the opposite pattern is found for glucose transporters and hexokinase transcripts; (2) Schistosomula contain low levels of transcripts encoding respiratory enzymes but regain the capacity for aerobic glucose metabolism as they mature to adulthood; (3) Male and female adults contain similar levels of the different transcripts involved in glucose metabolism.

Gene Expression Patterns in Larval Schistosoma mansoni Associated with Infection of the Mammalian Host

“…Citric acid cycle enzyme transcripts were consistently up-regulated in the cercaria; the highest change was 5 fold (citric acid cycle enzyme aconitase). This corroborates the findings of Skelly et al who showed that cercariae use aerobic metabolism, whereas schistosomula relied on glycolysis to supply energy [6], [41]. Given the extreme rapidity with which the cercarial tail oscillates and its limited glycogen store, the use of aerobic metabolism to yield the maximum possible molecules of ATP is optimal.…”

“…The cercarial tegument is known to be shed and replaced by the novel double bilayer structure [4] accompanied by the appearance of glucose transporters on the schistosomulum surface, doubtless to facilitate nutrient uptake [5]. The switch from aerobic to anaerobic metabolism has also been noted [6]. The highly sensitive methods now available to characterise gene expression present an opportunity to gain a deeper understanding of this important transition in the life cycle.…”

Schistosoma mansoni Sirtuins: Characterization and Potential as Chemotherapeutic Targets

“…Their cell division (for egg production) is intense and outside the control of the host, they are practically invisible to the host immune response. They also have a high level of metabolic activity, which like tumours, is dependent on the use of large amounts of glucose that is metabolized by aerobic glycolysis (culminating with the conversion of pyruvate to lactate rather than its use in oxidative phosphorylation) within the mammalian host [9], [10]. This type of metabolism was first shown to be a characteristic of cancer cells by Warburg [11].…”

Revisiting glucose uptake and metabolism in schistosomes: new molecular insights for improved schistosomiasis therapies

“…In tandem, schistosomes shift rapidly from the consumption of stored glycogen to a dependence on host glucose during the transformation phase from free-living cercariae to schistosomula (Skelly et al, 1993). In the mammalian stages, schistosomula have low expression of respiratory enzymes but regain their capacity for aerobic glucose metabolism as they develop to adult worms (Skelly and Shoemaker, 1995). Schistosomes express a range of mRNAs at relatively high levels associated with anaerobic and oxidative glucose metabolism during the transformation from cercaria to adult, re-emphasizing the fact that adult worms possess a significant capacity to generate energy through aerobic metabolism (Skelly et al, 1993).…”