In vitro and in vivo anti-piroplasm activity of PBT2 against Theileria annulata and Babesia microti

  • Int J Parasitol Drugs Drug Resist. 2026 Apr 22:31:100646. doi: 10.1016/j.ijpddr.2026.100646.
Jin Che  1 ,  Yixuan Wu  2 ,  Junwei Wang  2 ,  Yijun Chai  2 ,  Jinming Wang  2 ,  Wei Li  3 ,  Shuaiyang Zhao  4 ,  Guiquan Guan  5 ,  Hong Yin  6
Affiliations
  • 1. State Key Laboratory of Animal Disease Control and Prevention, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Xujiaping 1, Lanzhou, Gansu, 730046, China; College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150006, China.
  • 2. State Key Laboratory of Animal Disease Control and Prevention, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Xujiaping 1, Lanzhou, Gansu, 730046, China.
  • 3. College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150006, China.
  • 4. State Key Laboratory of Animal Disease Control and Prevention, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Xujiaping 1, Lanzhou, Gansu, 730046, China. Electronic address: [email protected].
  • 5. State Key Laboratory of Animal Disease Control and Prevention, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Xujiaping 1, Lanzhou, Gansu, 730046, China. Electronic address: [email protected].
  • 6. State Key Laboratory of Animal Disease Control and Prevention, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Xujiaping 1, Lanzhou, Gansu, 730046, China; Jiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, 225009, China. Electronic address: [email protected].
PMID: 42030593 DOI: 10.1016/j.ijpddr.2026.100646
Abstract

Theileriosis and babesiosis remain major constraints to livestock production, and increasing drug resistance necessitates alternative therapeutic strategies. Here, we evaluated the metal ionophore PBT2 for anti-piroplasm activity. PBT2 inhibited proliferation of two Theileria annulata schizont infected cell lines with IC50 values of 450.9 nM and 407.8 nM and significantly reduced Parasite burden. Colony formation was suppressed in both cell lines, consistent with parasite-associated growth inhibition. Cytotoxicity in BoMAC cells was limited, yielding a selectivity index exceeding 60-fold. ICP-MS analysis of purified schizonts showed dose-dependent Zn accumulation and concomitant Mn depletion following PBT2 treatment, whereas Cu and Fe levels were not significantly altered. In infected cells, PBT2 increased reactive oxygen species levels and reduced total superoxide dismutase activity. Partial restoration of viability by Mn supplementation supports a functional link between Mn depletion and growth inhibition. In a Babesia microti murine model, PBT2 reduced PEAK parasitemia in a dose-dependent manner and ameliorated infection-associated anemia. Our findings indicate PBT2 as a promising, safe, and broad-spectrum anti-piroplasm chemical compound that could be used to develop the drug formulation for controlling the infections of drug resistant piroplasm in future.

Keywords
Babesia microti; Drug resistance; PBT2; Theileria annulata.
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