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Metabolic drug targets of the cytosine metabolism pathways in the dromedary camel (Camelus dromedarius) and blood parasite Trypanosoma evansi

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Abstract

Trypanosomiasis is a major illness affecting camels in tropical and subtropical regions. Comparisons of camel and Trypanosoma evansi genomes can lead to the discovery of new drug targets for treating Trypanosoma infections. The synthesis pathways of cytosine, cytidine, cytidine monophosphate (CMP), cytidine diphosphate (CDP), cytidine triphosphate (CTP) deoxycytidine, deoxycytidine monophosphate (dCMP), deoxycytidine diphosphate (dCDP), and deoxycytidine triphosphate (dCTP) were compared in the dromedary camel (Camelus dromedarius) and T. evansi. None of the enzymes involved in cytosine pathway were detected in camels and T. evansi. Notably, cytidine kinase (CK) and 5′-nucleotidase, which interconverts cytidine to CMP, were not detected in T. evansi but were present in camels. UMP/CMP kinase was not predicted in T. evansi. Therefore, the presence of enzymes involved in the CTP synthesis cascade was not predicted in T. evansi. CMP synthesis might also be encoded by other enzymes, e.g., purine nucleotides kinases. Both camel and T. evansi share an efficient enzyme system for converting CDP to CTP. In conclusion, CTP synthase is important for homeostasis of cytosine nucleotides in T. evansi and could be a potential drug target against the parasite. In addition, the inhibition of UMP synthesis might contribute to parasite death as it is a shared source for CTP synthesis.

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Acknowledgements

The authors acknowledge the financial support of this project by King Abdul-Aziz City for Science and Technology (KACST), Basic Research Programs, National Transformation Program, under Research and Development Grants Program for National Research Institutions and Centers (GPURC), Kingdom of Saudi Arabia (Grant No. 2-17-04-004-0001).

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Authors and Affiliations

  1. Department of Biomedical Sciences, College of Veterinary Medicine, King Faisal University, Al-Ahsa, 31982, Saudi Arabia

    Mahmoud Kandeel & Abdulla Al-Taher

  2. Department of Pharmacology, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafrelsheikh, 35255, Egypt

    Mahmoud Kandeel

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  1. Mahmoud Kandeel
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  2. Abdulla Al-Taher
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Correspondence to Mahmoud Kandeel.

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This article belongs to the Topical Collection: Camelids

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Kandeel, M., Al-Taher, A. Metabolic drug targets of the cytosine metabolism pathways in the dromedary camel (Camelus dromedarius) and blood parasite Trypanosoma evansi. Trop Anim Health Prod 52, 3337–3358 (2020). https://doi.org/10.1007/s11250-020-02366-8

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