Un complexe moléculaire unique à l’origine de la motilité et de l’invasion des Apicomplexes

Frénal, Karine; Soldati‐Favre, Dominique

doi:10.1051/medsci/2013295015

Cited by 8 publications

(1 citation statement)

References 50 publications

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“…The IMC plays major roles in parasite intracellular replication, motility and host cell invasion 56 – 58 . The best studied group of IMC proteins are components of the motor complex—also referred to as the “glideosome” – in T. gondii 59 , 60 . This actin-myosin motor complex powers the required cell motility, and the proteins identified include myosins, tubulins, actins and glideosome-associated proteins.…”

Section: Resultsmentioning

confidence: 99%

The transcriptome from asexual to sexual in vitro development of Cystoisospora suis (Apicomplexa: Coccidia)

Cruz‐Bustos

Feix

Lyrakis

et al. 2022

Sci Rep

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The apicomplexan parasite Cystoisospora suis is an enteropathogen of suckling piglets with woldwide distribution. As with all coccidian parasites, its lifecycle is characterized by asexual multiplication followed by sexual development with two morphologically distinct cell types that presumably fuse to form a zygote from which the oocyst arises. However, knowledge of the sexual development of C. suis is still limited. To complement previous in vitro studies, we analysed transcriptional profiles at three different time points of development (corresponding to asexual, immature and mature sexual stages) in vitro via RNASeq. Overall, transcription of genes encoding proteins with important roles in gametes biology, oocyst wall biosynthesis, DNA replication and axonema formation as well as proteins with important roles in merozoite biology was identified. A homologue of an oocyst wall tyrosine rich protein of Toxoplasma gondii was expressed in macrogametes and oocysts of C. suis. We evaluated inhibition of sexual development in a host-free culture for C. suis by antiserum specific to this protein to evaluate whether it could be exploited as a candidate for control strategies against C. suis. Based on these data, targets can be defined for future strategies to interrupt parasite transmission during sexual development.

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Section: Resultsmentioning

confidence: 99%

The transcriptome from asexual to sexual in vitro development of Cystoisospora suis (Apicomplexa: Coccidia)

Cruz‐Bustos

Feix

Lyrakis

et al. 2022

Sci Rep

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Proteomic characterization of the subpellicular cytoskeleton of Toxoplasma gondii tachyzoites

León

Martín

Hernández

et al. 2014

Journal of Proteomics

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Identification of Novel, Potent, and Selective Compounds against Malaria Using Glideosomal-Associated Protein 50 as a Drug Target

Agrawal,

Kumari,

Mohmmed

et al. 2023

ACS Omega

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Phylum apicomplexan consists of parasites, such as Plasmodium and Toxoplasma. These obligate intracellular parasites enter host cells via an energy-dependent process using specialized machinery, called the glideosome. In the present study, we used Plasmodium falciparum GAP50, a glideosome-associated protein, as a target to screen 951 different compounds from diverse chemical libraries. Using different screening methods, eight compounds (Hayatinine, Curine, MMV689758 (Bedaquiline), MMV1634402 (Brilacidin), and MMV688271, MMV782353, MMV642550, and USINB4-124-8) were identified, which showed promising binding affinity (KD < 75 μM), along with submicromolar range antiparasitic efficacy and selectivity index > 100 fold for malaria parasite. These eight compounds were effective against Chloroquine-resistant PfINDO and Artemisinin-resistant PfCam3.1R359T strains. Studies on the effect of these compounds at asexual blood stages showed that these eight compounds act differently at different developmental stages, indicating the binding of these compounds to other Plasmodium proteins, in addition to PfGAP50. We further studied the effects of compounds (Bedaquiline and USINB4-124-8) in an in vivo Plasmodium berghei mouse model of malaria. Importantly, the oral delivery of Bedaquiline (50 mg/kg b. wt.) showed substantial suppression of parasitemia, and three out of seven mice were cured of the infection. Thus, our study provides new scaffolds for the development of antimalarials that can act at multiple Plasmodium lifecycle stages.

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Un complexe moléculaire unique à l’origine de la motilité et de l’invasion des Apicomplexes

Cited by 8 publications

References 50 publications

The transcriptome from asexual to sexual in vitro development of Cystoisospora suis (Apicomplexa: Coccidia)

The transcriptome from asexual to sexual in vitro development of Cystoisospora suis (Apicomplexa: Coccidia)

Proteomic characterization of the subpellicular cytoskeleton of Toxoplasma gondii tachyzoites

Identification of Novel, Potent, and Selective Compounds against Malaria Using Glideosomal-Associated Protein 50 as a Drug Target

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