Lumefantrine and o-choline – Parasite metabolism specific drug molecules inhibited in vitro growth of Theileria equi and Babesia caballi in MASP culture system

Maji, Chinmoy; Goel, Parveen; Suthar, Abhinav; Mandal, Kruti Debnath; Gopalakrishnan, A.; Kumar, Rajender; Tripathi, Bhupendra Nath; Kumar, Sanjay

doi:10.1016/j.ttbdis.2019.01.004

Cited by 5 publications

(4 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Various other chemotherapeutic agents have been reported to be potentially used against EP, with variable efficacy, mostly in vitro. Among these are anti-malaria compounds [37][38][39], antimicrobial agents [40][41][42][43][44][45], parasite metabolism inhibitors [34,[46][47][48][49][50][51][52][53], replication inhibitors [54,55], pyrimidine synthesis inhibitors [56,57], and various plant-derived compounds [58][59][60][61][62][63]. However, most of these options have never been tested in vivo, and none is widely used.…”

Section: Immunity Treatment and Controlmentioning

confidence: 99%

Twenty Years of Equine Piroplasmosis Research: Global Distribution, Molecular Diagnosis, and Phylogeny

et al. 2020

View full text Add to dashboard Cite

Equine piroplasmosis (EP), caused by the hemoparasites Theileria equi, Theileria haneyi, and Babesia caballi, is an important tick-borne disease of equines that is prevalent in most parts of the world. Infection may affect animal welfare and has economic impacts related to limitations in horse transport between endemic and non-endemic regions, reduced performance of sport horses and treatment costs. Here, we analyzed the epidemiological, serological, and molecular diagnostic data published in the last 20 years, and all DNA sequences submitted to GenBank database, to describe the current global prevalence of these parasites. We demonstrate that EP is endemic in most parts of the world, and that it is spreading into more temperate climates. We emphasize the importance of using DNA sequencing and genotyping to monitor the spread of parasites, and point to the necessity of further studies to improve genotypic characterization of newly recognized parasite species and strains, and their linkage to virulence.

show abstract

Section: Immunity Treatment and Controlmentioning

confidence: 99%

Twenty Years of Equine Piroplasmosis Research: Global Distribution, Molecular Diagnosis, and Phylogeny

et al. 2020

View full text Add to dashboard Cite

show abstract

“…We speculate that this entire ortholog group could have a conserved role in choline acquisition for the critical process of PC biosynthesis to support an intra-erythrocytic lifestyle. PC biosynthesis is the main biosynthetic process in blood stages of Babesia ( Florin-Christensen et al, 2000 ) and compounds that inhibit PC biosynthesis have been shown to have anti-parasite activity against Babesia and Theileria blood stages ( AbouLaila et al, 2014 ; Gopalakrishnan et al, 2016 ; Maji et al, 2019 ; Richier et al, 2006 ).…”

Section: Discussionmentioning

confidence: 99%

A choline-releasing glycerophosphodiesterase essential for phosphatidylcholine biosynthesis and blood stage development in the malaria parasite

Ramaprasad

Burda

Calvani

et al. 2022

eLife

View full text Add to dashboard Cite

The malaria parasite Plasmodium falciparum synthesizes significant amounts of phospholipids to meet the demands of replication within red blood cells. De novo phosphatidylcholine (PC) biosynthesis via the Kennedy pathway is essential, requiring choline that is primarily sourced from host serum lysophosphatidylcholine (lysoPC). LysoPC also acts as an environmental sensor to regulate parasite sexual differentiation. Despite these critical roles for host lysoPC, the enzyme(s) involved in its breakdown to free choline for PC synthesis are unknown. Here we show that a parasite glycerophosphodiesterase (PfGDPD) is indispensable for blood stage parasite proliferation. Exogenous choline rescues growth of PfGDPD-null parasites, directly linking PfGDPD function to choline incorporation. Genetic ablation of PfGDPD reduces choline uptake from lysoPC, resulting in depletion of several PC species in the parasite, whilst purified PfGDPD releases choline from glycerophosphocholine in vitro. Our results identify PfGDPD as a choline-releasing glycerophosphodiesterase that mediates a critical step in PC biosynthesis and parasite survival.

show abstract

“…Lumefantrine has been shown to have a prominent inhibition effect on P. vivax (sexual and asexual stages), P. falciparum , P. berghei , T. equi and B. caballi (Eibach et al ., 2012; Patil et al ., 2013; Gimode et al ., 2015; WorldWide Antimalarial Resistance Network (WWARN) Lumefantrine PK/PD Study Group, 2015; Maji et al ., 2019). The terminal elimination half-life of a drug is an important determinant of the propensity for an anti-malarial drug to select for resistance.…”

Section: Discussionmentioning

confidence: 99%

“…Lumefantrine also showed a good therapeutic effect on treating Plasmodium berghei , a developed lipidic system of lumefantrine exhibited excellent anti- P. berghei activity with 100% survival in male Swiss mice (Patil et al ., 2013). In addition, lumefantrine is used to treat apicomplexans such as Theileria equi and Babesia caballi recently (Maji et al ., 2019). As the first-line treatment of uncomplicated malaria caused by P. falciparum (WHO, 2010), lumefantrine was always combined with other agents, such as artemisinin, cepharanthine and atorvastatin (Desgrouas et al ., 2014; Dormoi et al ., 2014).…”

Section: Introductionmentioning

confidence: 99%

Determination of lumefantrine as an effective drug against Toxoplasma gondii infection – in vitro and in vivo study

et al. 2020

View full text Add to dashboard Cite

Toxoplasma gondii is an obligate intracellular protozoan parasite, which can infect almost all warm-blooded animals, including humans, leading to toxoplasmosis. Currently, the effective treatment for human toxoplasmosis is the combination of sulphadiazine and pyrimethamine. However, both drugs have serious side-effects and toxicity in the host. Therefore, there is an urgent need for the discovery of new anti-T. gondii drugs with high potency and less or no side-effects. Our findings suggest that lumefantrine exerts activity against T. gondii by inhibiting its proliferation in Vero cells in vitro without being toxic to Vero cells (P ≤ 0.01). Lumefantrine prolonged mice infected with T. gondii from death for 3 days at the concentration of 50 μg L−1 than negative control (phosphate-buffered saline treated only), and reduced the parasite burden in mouse tissues in vivo (P ≤ 0.01; P ≤ 0.05). In addition, a significant increase in interferon gamma (IFN-γ) production was observed in high-dose lumefantrine-treated mice (P ≤ 0.01), whereas interleukin 10 (IL-10) and IL-4 levels increased in low-dose lumefantrine-treated mice (P ≤ 0.01). The results demonstrated that lumefantrine may be a promising agent to treat toxoplasmosis, and more experiments on the protective mechanism of lumefantrine should be undertaken in further studies.

show abstract

Lumefantrine and o-choline – Parasite metabolism specific drug molecules inhibited in vitro growth of Theileria equi and Babesia caballi in MASP culture system

Cited by 5 publications

References 42 publications

Twenty Years of Equine Piroplasmosis Research: Global Distribution, Molecular Diagnosis, and Phylogeny

Twenty Years of Equine Piroplasmosis Research: Global Distribution, Molecular Diagnosis, and Phylogeny

A choline-releasing glycerophosphodiesterase essential for phosphatidylcholine biosynthesis and blood stage development in the malaria parasite

Determination of lumefantrine as an effective drug against Toxoplasma gondii infection – in vitro and in vivo study

Contact Info

Product

Resources

About