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Multiple pathways for glucose phosphate transport and utilization support growth of Cryptosporidium parvum

Rui Xu1,2, Wandy L Beatty1, Valentin Greigert1

  • 1Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, 63130, USA.

Nature Communications
|January 9, 2024
PubMed

Insights

Cryptosporidium parvum utilizes novel pathways for glucose uptake, directly importing glucose-6-phosphate and using glycogen phosphorylase to access stored carbohydrates, bypassing traditional hexokinase dependence.

Area of Science:

  • Parasitology
  • Molecular Biology
  • Biochemistry

Background:

  • Cryptosporidium parvum is an obligate intracellular parasite with a simplified mitochondrion.
  • The parasite relies on glycolysis for energy due to its inability to perform the tricarboxylic acid cycle or generate ATP.

Purpose of the Study:

  • To investigate the glucose uptake and metabolism pathways in Cryptosporidium parvum.
  • To understand how the parasite obtains phosphorylated hexose for glycolysis and carbohydrate storage.

Main Methods:

  • Genetic ablation experiments to assess the essentiality of glucose transporters (CpGT1, CpGT2) and hexokinase.
  • Complementation studies in E. coli to evaluate transporter function.
  • Enzyme activity assays for glycogen phosphorylase.

Main Results:

  • CpGT1 and CpGT2, along with hexokinase, were found to be dispensable for parasite growth.
  • Evidence suggests direct transport of glucose-6-phosphate into the parasite by CpGT1 and CpGT2.
  • The enzyme glycogen phosphorylase is essential for utilizing amylopectin stores.

Conclusions:

  • Cryptosporidium parvum employs multiple strategies to acquire phosphorylated glucose.
  • The parasite bypasses host hexokinase by directly importing glucose-6-phosphate.
  • Glycogen phosphorylase plays a critical role in accessing stored carbohydrates for parasite survival.

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