Metabolic drug targets of the cytosine metabolism pathways in the dromedary camel ( Camelus dromedarius ) and blood para
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Metabolic drug targets of the cytosine metabolism pathways in the dromedary camel (Camelus dromedarius) and blood parasite Trypanosoma evansi Mahmoud Kandeel 1,2
&
Abdulla Al-Taher 1
Received: 7 December 2019 / Accepted: 31 July 2020 # Springer Nature B.V. 2020
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. Keywords Camel . Trypanosoma evansi . Pyrimidine . Drug discovery . Cytosine . Cytidine
Introduction Trypanosomiasis is a devastating blood protozoal disease caused by multiple Trypanosoma species, which are transmitted by tsetse and other biting flies (Abdi et al., 2017). In humans, the two significant forms of trypanosomiasis are
This article belongs to the Topical Collection: Camelids Guest Editor: Bernard Faye * Mahmoud Kandeel [email protected] 1
Department of Biomedical Sciences, College of Veterinary Medicine, King Faisal University, Al-Ahsa 31982, Saudi Arabia
2
Department of Pharmacology, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafrelsheikh 35255, Egypt
African and American trypanosomiasis, which are termed sleeping sickness and Chagas disease, respectively. In animals, the disease is a significant health hazard with high economic impact (Ebhodaghe et al., 2018). Within the Trypanosoma genus, T. evansi has the highest distribution in the world and the widest potential affected hosts. The symptoms of infection with T. evansi are diverse and include recurrent fever, loss of appetite, loss of weight, poor body condition, jaundice, nervous signs, loss of production, and abortion (Desquesnes et al., 2013). It can be deadly, but the infected can also be asymptomatic or demonstrate mild signs such as poor body condition and performance de
