Archives

  • 2018-07
  • 2018-10
  • 2018-11
  • 2019-04
  • 2019-05
  • 2019-06
  • 2019-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2019-12
  • 2020-01
  • 2020-02
  • 2020-03
  • 2020-04
  • 2020-05
  • 2020-06
  • 2020-07
  • 2020-08
  • 2020-09
  • 2020-10
  • 2020-11
  • 2020-12
  • 2021-01
  • 2021-02
  • 2021-03
  • 2021-04
  • 2021-05
  • 2021-06
  • 2021-07
  • 2021-08
  • 2021-09
  • 2021-10
  • 2021-11
  • 2021-12
  • 2022-01
  • 2022-02
  • 2022-03
  • 2022-04
  • 2022-05
  • 2022-06
  • 2022-07
  • 2022-08
  • 2022-09
  • 2022-10
  • 2022-11
  • 2022-12
  • 2023-01
  • 2023-02
  • 2023-03
  • 2023-04
  • 2023-05
  • 2023-06
  • 2023-07
  • 2023-08
  • 2023-09
  • 2023-10
  • 2023-11
  • 2023-12
  • 2024-01
  • 2024-02
  • 2024-03
  • Theileria equi and Babesia caballi

    2020-08-04

    Theileria equi and Babesia caballi, are pear-shaped erythrocytic protozoan parasites that belong to the liothyronine sodium Theileriidae and Babesidae, members of the phylum Apicomplexa (OIE, 2008). These two parasites cause acute haemolytic anemia in horses, mules, donkeys and zebras, known as equine piroplasmosis (EP) (Rothschild, 2013). T. equi and B. caballi have many common tick vectors and frequently co-infect horses. Both are found globally where tick vectors are present, and are endemic to most tropical and subtropical areas as well as temperate climatic zones, including many parts of Europe, Africa, Arabia and Asia (except Japan) (Brünning, 1996). Infected horses remain seropositive for a period of several years (B. caballi) to a lifetime (B. caballi and T. equi) (Rothschild, 2013). However, active infection results in acute cases and death, which has a significant impact on the international movement of horses (Knowles, 1996). Economic losses associated with EP are significant and include the cost of treatment, especially in acutely infected horses, abortion in the last trimester of gestation, loss of performance, death, and restrictions in meeting international requirements related to exportation or participation in equestrian sporting events (DE Waal, 1992, Kerber et al., 1999, Lewis et al., 1999). T. equi reported resistant to babecidal drugs (Brünning, 1996), while diminazene aceturate treatment in horses and mules results in mild to severe toxicity (Tuntasuvan et al., 2003). Therefore, an alternative chemotherapeutic drug is needed for control of EP. Dihydroorotate dehydrogenase (DHODH) is the fourth enzyme in the de novo pyrimidine biosynthesis pathway, essential for survival of apicomplexan parasites by providing UMP, which is essential for RNA and DNA synthesis (Shambaugh, 1979, Phillips et al., 2008). DHODH inhibitors have been studied for treatment of various pathogens. For example, redoxal, dichloroallyl lawsone (DCL), and three analogs of A77 1726, DHODH liothyronine sodium inhibitors were tested with Plasmodium falciparum (Baldwin et al., 2002). The A77-1726, leflunomide, MD249 and MD209 compounds were evaluated on the inhibition of Toxoplasma gondii DHODH (TgDHODH) (Hortua Triana et al., 2012). Leflunomide has been studied as a drug for treatment of arthritis (McRobert and McConkey, 2002). The quinone co-substrate of the dihydroorotate dehydrogenase, atovaquone, is active against Plasmodium, Toxoplasma gondii (Baggish and Hill, 2002), Babesia spp. (Weiss, 2002) and Babesia gibsoni (Matsuu et al., 2004). Atovaquone was verified to be used for the therapeutic window (efficacy versus toxicity), as it was an uncompetitive inhibitor of human DHODH and a non-competitive inhibitor of the rat DHODH (Knecht et al., 2000). Brequinar derivatives were also proved as potentially effective inhibitors against P. falciparum DHODH (Hurt et al., 2006). Our previous study showed that DHODH inhibitors effectively inhibited the activity of rBboDHODH as well as the growth of Babesia bovis in vitro. (Kamyingkird et al., 2014). However, currently there is no literature evaluating DHODH inhibitors as novel chemotherapeutic drug for EP. In the present study, we compared T. equi DHODH to other apicomplexan protozoa DHODHs using bioinformatics and immunoblot analysis. In addtion, DHODH inhibitors were evaluated for inhibition of T. equi and B. caballi by in vitro inhibition assay.