The cytosolic tryparedoxin of Leishmania infantum is essential for parasite survival

• Type: Article in International Scientific Journal
• Date: 2009

Authors

romao, s (Author) Other; castro, h (Author) Other; sousa, c (Author) Other; carvalho, s (Author) Other; tomas, am (Author) ICBAS

Journal

Title: International Journal for Parasitology

Vol. 39

Pages: 703-711

ISSN: 0020-7519

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 23 Citations

Scopus - 26 Citations

Scientific classification

FOS: Medical and Health sciences > Health sciences

Other information

Authenticus ID: P-003-KD7

DOI: 10.1016/j.ijpara.2008.11.009

Abstract (EN): Leishmania infantum cytosolic tryparedoxin (LiTXN1) can be regarded as a potential candidate for drug targeting. This redox active molecule, which belongs to the thioredoxin superfamily, is one constituent of the hydroperoxide elimination cascade in L infantum and may also be involved in other cellular processes such as DNA synthesis or host-parasite interaction. In order to validate LiTXN1 as a drug target we have employed a gene replacement strategy. We observed that substitution of both chromosomal LiTXN1 alleles was only possible upon parasite complementation with an episomal copy of the gene. Furthermore, contrary to control parasites carrying the empty vector, both the insect and the mammalian stages of L infantum retained the episomal copy of LiTXN1 in the absence of drug pressure. These results confirm the essentiality of LiTXN1 throughout the life cycle of the parasite, namely in the disease-causing amastigote stage. In addition, the data obtained showed that disruption of one allele of this gene leads only to a 25% reduction in the expression of LiTXN1. Even though this does not affect promastigote growth and susceptibility to hydrogen peroxide, ex vivo infection assays suggest that wild-type levels of LiTXN1 are required for optimal L infantum virulence. (C) 2008 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9