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

Author

Listed:
  • Rui Xu

    (Washington University School of Medicine
    South China Agricultural University)

  • Wandy L. Beatty

    (Washington University School of Medicine)

  • Valentin Greigert

    (Washington University School of Medicine)

  • William H. Witola

    (University of Illinois Urbana-Champaign)

  • L. David Sibley

    (Washington University School of Medicine)

Abstract

Cryptosporidium parvum is an obligate intracellular parasite with a highly reduced mitochondrion that lacks the tricarboxylic acid cycle and the ability to generate ATP, making the parasite reliant on glycolysis. Genetic ablation experiments demonstrated that neither of the two putative glucose transporters CpGT1 and CpGT2 were essential for growth. Surprisingly, hexokinase was also dispensable for parasite growth while the downstream enzyme aldolase was required, suggesting the parasite has an alternative way of obtaining phosphorylated hexose. Complementation studies in E. coli support a role for direct transport of glucose-6-phosphate from the host cell by the parasite transporters CpGT1 and CpGT2, thus bypassing a requirement for hexokinase. Additionally, the parasite obtains phosphorylated glucose from amylopectin stores that are released by the action of the essential enzyme glycogen phosphorylase. Collectively, these findings reveal that C. parvum relies on multiple pathways to obtain phosphorylated glucose both for glycolysis and to restore carbohydrate reserves.

Suggested Citation

  • Rui Xu & Wandy L. Beatty & Valentin Greigert & William H. Witola & L. David Sibley, 2024. "Multiple pathways for glucose phosphate transport and utilization support growth of Cryptosporidium parvum," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-44696-3
    DOI: 10.1038/s41467-024-44696-3
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    References listed on IDEAS

    as
    1. Ping Xu & Giovanni Widmer & Yingping Wang & Luiz S. Ozaki & Joao M. Alves & Myrna G. Serrano & Daniela Puiu & Patricio Manque & Donna Akiyoshi & Aaron J. Mackey & William R. Pearson & Paul H. Dear & A, 2004. "Correction: Corrigendum: The genome of Cryptosporidium hominis," Nature, Nature, vol. 432(7015), pages 415-415, November.
    2. Ping Xu & Giovanni Widmer & Yingping Wang & Luiz S. Ozaki & Joao M. Alves & Myrna G. Serrano & Daniela Puiu & Patricio Manque & Donna Akiyoshi & Aaron J. Mackey & William R. Pearson & Paul H. Dear & A, 2004. "The genome of Cryptosporidium hominis," Nature, Nature, vol. 431(7012), pages 1107-1112, October.
    3. Casey M. Theriot & Mark J. Koenigsknecht & Paul E. Carlson & Gabrielle E. Hatton & Adam M. Nelson & Bo Li & Gary B. Huffnagle & Jun Z. Li & Vincent B. Young, 2014. "Antibiotic-induced shifts in the mouse gut microbiome and metabolome increase susceptibility to Clostridium difficile infection," Nature Communications, Nature, vol. 5(1), pages 1-10, May.
    4. Phuong N. Tran & Simon H. J. Brown & Todd W. Mitchell & Kai Matuschewski & Paul J. McMillan & Kiaran Kirk & Matthew W. A. Dixon & Alexander G. Maier, 2014. "A female gametocyte-specific ABC transporter plays a role in lipid metabolism in the malaria parasite," Nature Communications, Nature, vol. 5(1), pages 1-13, December.
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