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A novel protein kinase is essential in bloodstream Trypanosoma brucei.

ABSTRACT: Human African trypanosomiasis a fatal disease for which no vaccines exist and treatment regimens are difficult. Here, we evaluate a Trypanosoma brucei protein kinase, AEK1, as a potential drug target. Conditional knockouts confirmed AEK1 essentiality in bloodstream forms. For chemical validation, we overcame the lack of AEK1 inhibitors by creating parasites expressing a single, functional analog-sensitive AEK1 allele. Analog treatment of mice infected with this strain delayed parasitemia and death, with one-third of animals showing no parasitemia. These studies validate AEK1 as a drug target and highlight the need for further understanding of its function.

SUBMITTER: Jensen BC

PROVIDER: S-EPMC4925258 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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A novel protein kinase is essential in bloodstream Trypanosoma brucei.

Jensen Bryan C BC Booster Nick N Vidadala Rama Subba Rao RS Maly Dustin J DJ Parsons Marilyn M

International journal for parasitology 20160323 8

Human African trypanosomiasis a fatal disease for which no vaccines exist and treatment regimens are difficult. Here, we evaluate a Trypanosoma brucei protein kinase, AEK1, as a potential drug target. Conditional knockouts confirmed AEK1 essentiality in bloodstream forms. For chemical validation, we overcame the lack of AEK1 inhibitors by creating parasites expressing a single, functional analog-sensitive AEK1 allele. Analog treatment of mice infected with this strain delayed parasitemia and dea ...[more]

PMID: 27018127

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