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

Rui Xu1, Wandy L Beatty1, Valentin Greigert1

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

Biorxiv : the Preprint Server for Biology
|July 10, 2023
PubMed

Insights

Cryptosporidium parvum utilizes multiple pathways to acquire phosphorylated glucose, bypassing traditional host cell glucose uptake and hexokinase activity. This parasite obtains glucose-6-phosphate directly from the host and from internal amylopectin stores.

Area of Science:

  • Parasitology
  • Molecular Biology
  • Biochemistry

Background:

  • Cryptosporidium parvum is an obligate intracellular parasite reliant on glycolysis due to its reduced mitochondrion.
  • The parasite's energy metabolism and glucose acquisition pathways remain incompletely understood.

Approach:

  • Genetic ablation experiments were used to assess the essentiality of glucose transporters (CpGT1, CpGT2) and hexokinase.
  • Complementation studies in E. coli investigated the function of CpGT1 and CpGT2.
  • The role of glycogen phosphorylase in utilizing internal carbohydrate reserves was examined.

Key Points:

  • Neither CpGT1 nor CpGT2, nor hexokinase, were essential for parasite growth.
  • CpGT1 and CpGT2 can directly transport glucose-6-phosphate from the host cell.
  • The parasite utilizes glycogen phosphorylase to access phosphorylated glucose from amylopectin stores.

Conclusions:

  • Cryptosporidium parvum employs alternative strategies for obtaining phosphorylated glucose.
  • These strategies include direct host cell glucose-6-phosphate uptake and mobilization of internal amylopectin reserves.
  • These findings reveal novel metabolic adaptations crucial for parasite survival and pathogenesis.
Keywords:
energy utilizationglucose phosphate transportglucose transportglycogenglycolysis

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