Disruption of the trypanothione reductase gene of Leishmania decreases its ability to survive oxidative stress in macrophages

The EMBO Journal
C DumasB Papadopoulou

Abstract

Parasitic protozoa belonging to the order Kinetoplastida contain trypanothione as their major thiol. Trypanothione reductase (TR), the enzyme responsible for maintaining trypanothione in its reduced form, is thought to be central to the redox defence systems of trypanosomatids. To investigate further the physiological role of TR in Leishmania, we attempted to create TR-knockout mutants by gene disruption in L. donovani and L. major strains using the selectable markers neomycin and hygromycin phosphotransferases. TR is likely to be an important gene for parasite survival since all our attempts to obtain a TR null mutant in L. donovani failed. Instead, we obtained mutants with a partial trisomy for the TR locus where, despite the successful disruption of two TR alleles by gene targeting, a third TR copy was generated as a result of genomic rearrangements involving the translocation of a TR-containing region to a larger chromosome. Mutants of L. donovani and L. major possessing only one wild-type TR allele express less TR mRNA and have lower TR activity compared with wild-type cells carrying two copies of the TR gene. Significantly, these mutants show attenuated infectivity with a markedly decreased capacity to survive intracellul...Continue Reading

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Citations

Sep 17, 2009·Applied Biochemistry and Biotechnology·Anil Kumar ShuklaVikash Kumar Dubey
Apr 29, 2011·Journal of Parasitic Diseases : Official Organ of the Indian Society for Parasitology·Bhavna Chawla, Rentala Madhubala
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