In vitro and in vivo effects of the phytohormone inhibitor fluridone against Neospora caninum infection.
Neospora caninum causes abortion and stillbirth in cattle. Identification of effective drugs against this parasite remains a challenge. Previous studies have suggested that disruption of abscisic acid (ABA)-mediated signaling in apicomplexan parasites such as Toxoplasma gondii offers a new drug target. In this study, the ABA inhibitor, fluridone (FLU), was evaluated for its action against N. caninum. Production of endogenous ABA within N. caninum was confirmed by ultra-performance liquid chromatography-tandem quadruple mass spectrometry. Subsequently, FLU treatment efficacy was assessed using in vitro. Results revealed that FLU inhibited the growth of N. caninum and T. gondii in vitro (IC50 143.1±43.96μM and 330.6±52.38μM, respectively). However, FLU did not affect parasite replication at 24h post-infection, but inhibited egress of N. caninum thereafter. To evaluate the effect of FLU in vivo, N. caninum-infected mice were treated with FLU for 15days. FLU treatment appeared to ameliorate acute neosporosis induced by lethal parasite challenge. Together, our data shows that ABA might control egress in N. caninum. Therefore, FLU has potential as a candidate drug for the treatment of acute neosporosis.
['Ybañez|Rochelle Haidee D|RH|', 'Leesombun|Arpron|A|', 'Nishimura|Maki|M|', 'Matsubara|Ryuma|R|', 'Kojima|Mikiko|M|', 'Sakakibara|Hitoshi|H|', 'Nagamune|Kisaburo|K|', 'Nishikawa|Yoshifumi|Y|']
D000040:Abscisic Acid D000818:Animals D002417:Cattle D002418:Cattle Diseases D003048:Coccidiosis D005260:Female D051379:Mice D008807:Mice, Inbred BALB C D018688:Neospora D010937:Plant Growth Regulators D011247:Pregnancy D011248:Pregnancy Complications D011728:Pyridones D013047:Specific Pathogen-Free Organisms D050497:Stillbirth
Fluridone Neospora caninum Abscisic acid