Functional characterization of a unique cytochrome P450 in  Toxoplasma gondii

Xiao Zhang; Taotao Zhang; Jing Liu; Muzi Li; Yong Fu; Jianhai Xu; Qun Liu

doi:10.18632/oncotarget.23023

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Research Papers:

Functional characterization of a unique cytochrome P450 in Toxoplasma gondii

Xiao Zhang, Taotao Zhang, Jing Liu, Muzi Li, Yong Fu, Jianhai Xu and Qun Liu _

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Oncotarget. 2017; 8:115079-115088. https://doi.org/10.18632/oncotarget.23023

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Abstract

Xiao Zhang1,2, Taotao Zhang1,2, Jing Liu1,2, Muzi Li1,2, Yong Fu1,2, Jianhai Xu1,2 and Qun Liu1,2

1Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, China

2National Animal Protozoa Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing, China

Correspondence to:

Qun Liu, email: [email protected]

Keywords: T. gondii; P450; biotransformation enzymes; drug resistance

Received: October 09, 2017 Accepted: November 15, 2017 Published: December 06, 2017

ABSTRACT

The basic metabolic cytochrome P450 (CYP) proteins are essential for the biotransformation of sterols and xenobiotics. By contrast, the Toxoplasma gondii genome contains only one CYP gene, and the role of this enzyme in the physiology and biochemistry of apicomplexan parasites is unknown. Because it is a potential resistance gene, identifying the functionality of P450 in T. gondii is particularly important. Knocking out Tg-P450 had no significant effect on T. gondii survival, but mice infected with parasites overexpressing Tg-P450 exhibited significantly enhanced pathogenicity. Enzyme activity analyses demonstrated that this protein has mammalian CYP2B and CYP3A enzymatic activity. In addition, T. gondii lacking the P450 gene exhibited reduced resistance to quinine, mefloquine and clarithromycin compared with parasites overexpressing Tg-P450. These results suggest that P450 functions in T. gondii metabolism and detoxification is involved in vitally important processes in parasitic organisms, making this enzyme a potential drug target.

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Research Papers:

Functional characterization of a unique cytochrome P450 in Toxoplasma gondii

Abstract