Plant-Type Trehalose Synthetic Pathway in Cryptosporidium and Some Other ApicomplexansReportar como inadecuado




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Background

The trehalose synthetic pathway is present in bacteria, fungi, plants and invertebrate animals, but is absent in vertebrates. This disaccharide mainly functions as a stress protectant against desiccation, heat, cold and oxidation. Genes involved in trehalose synthesis have been observed in apicomplexan parasites, but little was known about these enzymes. Study on trehalose synthesis in apicomplexans would not only shed new light into the evolution of this pathway, but also provide data for exploring this pathway as novel drug target.

Methodology-Principal Findings

We have observed the presence of the trehalose synthetic pathway in Cryptosporidium and other apicomplexans and alveolates. Two key enzymes trehalose 6-phosphate synthase T6PS; EC 2.4.1.15 and trehalose phosphatase TPase; EC 3.1.3.12 are present as Class II bifunctional proteins T6PS-TPase in the majority of apicomplexans with the exception of Plasmodium species. The enzyme for synthesizing the precursor UDP-glucose is homologous to dual-substrate UDP-galactose-glucose pyrophosphorylases UGGPases, rather than the -classic- UDP-glucose pyrophosphorylase UGPase. Phylogenetic recontructions indicate that both T6PS-TPases and UGGPases in apicomplexans and other alveolates are evolutionarily affiliated with stramenopiles and plants. The expression level of T6PS-TPase in C. parvum is highly elevated in the late intracellular developmental stage prior to or during the production of oocysts, implying that trehalose may be important in oocysts as a protectant against environmental stresses. Finally, trehalose has been detected in C. parvum oocysts, thus confirming the trehalose synthetic activity in this parasite.

Conclusions-Significance

A trehalose synthetic pathway is described in the majority of apicomplexan parasites including Cryptosporidium and the presence of trehalose was confirmed in the C. parvum oocyst. Key enzymes in the pathway i.e., T6PS-TPase and UGGPase are plant-type and absent in humans and animals, and may potentially serve as novel drug targets in the apicomplexans.



Autor: Yonglan Yu, Haili Zhang, Guan Zhu

Fuente: http://plos.srce.hr/



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