2. Academic Validation
  3. Anti-Toxoplasma activity of NBMPR is mediated through the inhibition of nucleoside and nucleobase transporters

Anti-Toxoplasma activity of NBMPR is mediated through the inhibition of nucleoside and nucleobase transporters

  • Parasitol Res. 2026 Feb 16;125(1):25. doi: 10.1007/s00436-026-08646-w.
Ming Pan 1 2 3,  Shu-Qin Tang 4,  Ceng-Ceng Ge 4,  Shi-Jie Fan 4,  He-Xin He 4,  Man-Man Bian 4,  Bang Shen 5,  Si-Yang Huang 6 7 8
Affiliations

Affiliations

  • 1 College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu Province, PR China. [email protected].
  • 2 Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, 225009, PR China. [email protected].
  • 3 Joint International Research Laboratory of Agriculture and Agri-Product Safety, Ministry of Education of China, Yangzhou University, Yangzhou, 225009, PR China. [email protected].
  • 4 College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu Province, PR China.
  • 5 State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei Province, PR China.
  • 6 College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu Province, PR China. [email protected].
  • 7 Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, 225009, PR China. [email protected].
  • 8 Joint International Research Laboratory of Agriculture and Agri-Product Safety, Ministry of Education of China, Yangzhou University, Yangzhou, 225009, PR China. [email protected].
PMID: 41692887 DOI: 10.1007/s00436-026-08646-w
Abstract

Toxoplasma gondii stands among nature’s most successful eukaryotic pathogens, a status achieved through refined mechanisms for intracellular survival that enable pan-vertebrate host tropism. This ecological dominance derives principally from evolutionary refinements in metabolic plasticity, a modular integration of de novo biosynthesis with high-efficiency nutrient scavenging systems. The pyrimidine biosynthesis pathway is indispensable for robust Parasite proliferation. Our previous work demonstrated that exogenous uracil supplementation bypasses the DHO deficiency-induced growth restriction. Here, we reconfirm the functional pyrimidine rescue using an ATC-knockout Parasite line, identifying a protective salvage route that maintains pyrimidine pool homeostasis. Pharmacological suppression of T. gondii growth with NBMPR, a potent hENT1 antagonist, confirms that host hENT1 serves as a critical conduit for pyrimidine and purine acquisition by the Parasite. Evolutionary analysis identifies TgENT1, TgENT3, TGGT1_359630, and TgAT1 as hENT1 homologs, with TgENT1 demonstrating the strongest phylogenetic clustering with hENT1. The computational models predict interactions between TgENT1 and a spectrum of ligands (NBMPR, nucleosides, and nucleobases), supporting its classification as a broad-specificity nucleoside/nucleobase transporter, consistent with the function of hENT1. The genetic intractability of TgENT1, however, indicates that it likely plays an essential role in Parasite proliferation. Our study reveals that NBMPR-mediated inhibition of both TgENT1 and hENT1 disrupts a hierarchical transport cascade essential for T. gondii to acquire pyrimidines and purines from the host, highlighting the promise of a strategy that simultaneously targets both Parasite and host nutrient acquisition pathways for improved anti-toxoplasmosis therapy.

Keywords

TgENT1; Toxoplasma gondii; NBMPR; Nucleoside and nucleobase transporter; hENT1.

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