Elevated levels of tryparedoxin peroxidase in antimony unresponsive Leishmania donovani field isolates

Susan Wyllie; Goutam Mandal; Neeloo Singh; Shyam Sundar; Alan H. Fairlamb; Mitali Chatterjee

doi:10.1016/j.molbiopara.2010.05.015

Elevated levels of tryparedoxin peroxidase in antimony unresponsive Leishmania donovani field isolates

Susan Wyllie, Goutam Mandal, Neeloo Singh, Shyam Sundar, Alan H. Fairlamb, Mitali Chatterjee

Research output: Contribution to journal › Article › peer-review

66 Citations (Scopus)

Abstract

Enhancement of the anti-oxidant metabolism of Leishmania parasites, dependent upon the unique dithiol trypanothione, has been implicated in laboratory-generated antimony resistance. Here, the role of the trypanothione-dependent anti-oxidant pathway is studied in antimony-resistant clinical isolates. Elevated levels of tryparedoxin and tryparedoxin peroxidase, key enzymes in hydroperoxide detoxification, were observed in antimonial resistant parasites resulting in an increased metabolism of peroxides. These data suggest that enhanced anti-oxidant defences may play a significant role in clinical resistance to antimonials. (C) 2010 Elsevier B.V. All rights reserved.

Original language	English
Pages (from-to)	162-164
Number of pages	3
Journal	Molecular and Biochemical Parasitology
Volume	173
Issue number	2
DOIs	https://doi.org/10.1016/j.molbiopara.2010.05.015
Publication status	Published - Oct 2010

Keywords

Antimonial resistance
Leishmania donovani
Tryparedoxin peroxidase
ARSENITE-RESISTANT LEISHMANIA
GAMMA-GLUTAMYLCYSTEINE SYNTHETASE
DRUG-RESISTANCE
ORNITHINE-DECARBOXYLASE
PARASITIC PROTOZOA
TRYPANOTHIONE
METABOLISM
GENE
OVEREXPRESSION
EXPRESSION

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10.1016/j.molbiopara.2010.05.015

Aref#d: 18185. Characterization and validation of drug targets in the Kinetoplastida (Principal Research Fellowship/Programme Grant)
Fairlamb, A. (Investigator)
1/10/06 → 30/09/17
Project: Research

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@article{475dce1b52a74c02bce7235340a6a02f,

title = "Elevated levels of tryparedoxin peroxidase in antimony unresponsive Leishmania donovani field isolates",

abstract = "Enhancement of the anti-oxidant metabolism of Leishmania parasites, dependent upon the unique dithiol trypanothione, has been implicated in laboratory-generated antimony resistance. Here, the role of the trypanothione-dependent anti-oxidant pathway is studied in antimony-resistant clinical isolates. Elevated levels of tryparedoxin and tryparedoxin peroxidase, key enzymes in hydroperoxide detoxification, were observed in antimonial resistant parasites resulting in an increased metabolism of peroxides. These data suggest that enhanced anti-oxidant defences may play a significant role in clinical resistance to antimonials. (C) 2010 Elsevier B.V. All rights reserved.",

keywords = "Antimonial resistance, Leishmania donovani, Tryparedoxin peroxidase, ARSENITE-RESISTANT LEISHMANIA, GAMMA-GLUTAMYLCYSTEINE SYNTHETASE, DRUG-RESISTANCE, ORNITHINE-DECARBOXYLASE, PARASITIC PROTOZOA, TRYPANOTHIONE, METABOLISM, GENE, OVEREXPRESSION, EXPRESSION",

author = "Susan Wyllie and Goutam Mandal and Neeloo Singh and Shyam Sundar and Fairlamb, {Alan H.} and Mitali Chatterjee",

year = "2010",

month = oct,

doi = "10.1016/j.molbiopara.2010.05.015",

language = "English",

volume = "173",

pages = "162--164",

journal = "Molecular and Biochemical Parasitology",

issn = "0166-6851",

publisher = "Elsevier",

number = "2",

}

TY - JOUR

T1 - Elevated levels of tryparedoxin peroxidase in antimony unresponsive Leishmania donovani field isolates

AU - Wyllie, Susan

AU - Mandal, Goutam

AU - Singh, Neeloo

AU - Sundar, Shyam

AU - Fairlamb, Alan H.

AU - Chatterjee, Mitali

PY - 2010/10

Y1 - 2010/10

N2 - Enhancement of the anti-oxidant metabolism of Leishmania parasites, dependent upon the unique dithiol trypanothione, has been implicated in laboratory-generated antimony resistance. Here, the role of the trypanothione-dependent anti-oxidant pathway is studied in antimony-resistant clinical isolates. Elevated levels of tryparedoxin and tryparedoxin peroxidase, key enzymes in hydroperoxide detoxification, were observed in antimonial resistant parasites resulting in an increased metabolism of peroxides. These data suggest that enhanced anti-oxidant defences may play a significant role in clinical resistance to antimonials. (C) 2010 Elsevier B.V. All rights reserved.

AB - Enhancement of the anti-oxidant metabolism of Leishmania parasites, dependent upon the unique dithiol trypanothione, has been implicated in laboratory-generated antimony resistance. Here, the role of the trypanothione-dependent anti-oxidant pathway is studied in antimony-resistant clinical isolates. Elevated levels of tryparedoxin and tryparedoxin peroxidase, key enzymes in hydroperoxide detoxification, were observed in antimonial resistant parasites resulting in an increased metabolism of peroxides. These data suggest that enhanced anti-oxidant defences may play a significant role in clinical resistance to antimonials. (C) 2010 Elsevier B.V. All rights reserved.

KW - Antimonial resistance

KW - Leishmania donovani

KW - Tryparedoxin peroxidase

KW - ARSENITE-RESISTANT LEISHMANIA

KW - GAMMA-GLUTAMYLCYSTEINE SYNTHETASE

KW - DRUG-RESISTANCE

KW - ORNITHINE-DECARBOXYLASE

KW - PARASITIC PROTOZOA

KW - TRYPANOTHIONE

KW - METABOLISM

KW - GENE

KW - OVEREXPRESSION

KW - EXPRESSION

U2 - 10.1016/j.molbiopara.2010.05.015

DO - 10.1016/j.molbiopara.2010.05.015

M3 - Article

C2 - 20553768

SN - 0166-6851

VL - 173

SP - 162

EP - 164

JO - Molecular and Biochemical Parasitology

JF - Molecular and Biochemical Parasitology

IS - 2

ER -

Elevated levels of tryparedoxin peroxidase in antimony unresponsive Leishmania donovani field isolates

Abstract

Keywords

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Projects

Aref#d: 18185. Characterization and validation of drug targets in the Kinetoplastida (Principal Research Fellowship/Programme Grant)

Cite this