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Critical importance of the de novo pyrimidine biosynthesis pathway for Trypanosoma cruzi growth in the mammalian host cell cytoplasm.

Abstract：

:The intracellular parasitic protist Trypanosoma cruzi is the causative agent of Chagas disease in Latin America. In general, pyrimidine nucleotides are supplied by both de novo biosynthesis and salvage pathways. While epimastigotes-an insect form-possess both activities, amastigotes-an intracellular replicating form of T. cruzi-are unable to mediate the uptake of pyrimidine. However, the requirement of de novo pyrimidine biosynthesis for parasite growth and survival has not yet been elucidated. Carbamoyl-phosphate synthetase II (CPSII) is the first and rate-limiting enzyme of the de novo biosynthetic pathway, and increased CPSII activity is associated with the rapid proliferation of tumor cells. In the present study, we showed that disruption of the T. cruzi cpsII gene significantly reduced parasite growth. In particular, the growth of amastigotes lacking the cpsII gene was severely suppressed. Thus, the de novo pyrimidine pathway is important for proliferation of T. cruzi in the host cell cytoplasm and represents a promising target for chemotherapy against Chagas disease.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Hashimoto M,Morales J,Fukai Y,Suzuki S,Takamiya S,Tsubouchi A,Inoue S,Inoue M,Kita K,Harada S,Tanaka A,Aoki T,Nara T

doi

10.1016/j.bbrc.2011.12.073

subject

Has Abstract

pub_date

2012-01-20 00:00:00

pages

1002-6

issue

3

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(11)02282-0

journal_volume

417

pub_type

杂志文章

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