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Identification of proteins exhibiting TgDegP2-responsive thermal stability

ABSTRACT: To broadly explore artemisinin susceptibility in apicomplexan parasites, we used genome-scale CRISPR screens recently developed for Toxoplasma gondii to discover sensitizing and desensitizing mutations. From these screens, we identified the mitochondrial protease DegP2, which appeared gDegP2-responsive thermal stability in a pathway leading to decreased DHA susceptibility. To identify proteins exhibiting DegP2-responsive thermal stability

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Toxoplasma Gondii Gt1

SUBMITTER: Alice Herneisen

LAB HEAD: Sebastian Lourido

PROVIDER: PXD019917 | Pride | 2020-08-28

REPOSITORIES: Pride

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Genetic screens reveal a central role for heme metabolism in artemisinin susceptibility.

Harding Clare R CR Sidik Saima M SM Petrova Boryana B Gnädig Nina F NF Okombo John J Herneisen Alice L AL Ward Kurt E KE Markus Benedikt M BM Boydston Elizabeth A EA Fidock David A DA Lourido Sebastian S

Nature communications 20200923 1

Artemisinins have revolutionized the treatment of Plasmodium falciparum malaria; however, resistance threatens to undermine global control efforts. To broadly explore artemisinin susceptibility in apicomplexan parasites, we employ genome-scale CRISPR screens recently developed for Toxoplasma gondii to discover sensitizing and desensitizing mutations. Using a sublethal concentration of dihydroartemisinin (DHA), we uncover the putative transporter Tmem14c whose disruption increases DHA susceptibil ...[more]

PMID: 32968076

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