The GPI biosynthetic pathway as a therapeutic target for African sleeping sickness

Michael A. J. Ferguson; John S. Brimacombe; Jillian R. Brown; Arthur Crossman; Alexander Dix; Robert A. Field; M. Lucia S. Guther; Kenneth G. Milne; Deepak K. Sharma; Terry K. Smith

doi:10.1016/S0925-4439(99)00058-7

The GPI biosynthetic pathway as a therapeutic target for African sleeping sickness

Michael A. J. Ferguson, John S. Brimacombe, Jillian R. Brown, Arthur Crossman, Alexander Dix, Robert A. Field, M. Lucia S. Guther, Kenneth G. Milne, Deepak K. Sharma, Terry K. Smith

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

128 Citations (Scopus)

Abstract

African sleeping sickness is a debilitating and often fatal disease caused by tsetse fly transmitted African trypanosomes. These extracellular protozoan parasites survive in the human bloodstream by virtue of a dense cell surface coat made of variant surface glycoprotein. The parasites have a repertoire of several hundred immunologically distinct variant surface glycoproteins and they evade the host immune response by antigenic variation. All variant surface glycoproteins are anchored to the plasma membrane via glycosylphosphatidylinositol membrane anchors and compounds that inhibit the assembly or transfer of these anchors could have trypanocidal potential. This article compares glycosylphosphatidylinositol biosynthesis in African trypanosomes and mammalian cells and identifies several steps that could be targets for the development of parasite-specific therapeutic agents. (C) 1999 Elsevier Science B.V. All rights reserved.

Original language	English
Pages (from-to)	327-340
Number of pages	14
Journal	BBA - Molecular Basis of Disease
Volume	1455
Issue number	2-3
DOIs	https://doi.org/10.1016/S0925-4439(99)00058-7
Publication status	Published - 1999

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title = "The GPI biosynthetic pathway as a therapeutic target for African sleeping sickness",

abstract = "African sleeping sickness is a debilitating and often fatal disease caused by tsetse fly transmitted African trypanosomes. These extracellular protozoan parasites survive in the human bloodstream by virtue of a dense cell surface coat made of variant surface glycoprotein. The parasites have a repertoire of several hundred immunologically distinct variant surface glycoproteins and they evade the host immune response by antigenic variation. All variant surface glycoproteins are anchored to the plasma membrane via glycosylphosphatidylinositol membrane anchors and compounds that inhibit the assembly or transfer of these anchors could have trypanocidal potential. This article compares glycosylphosphatidylinositol biosynthesis in African trypanosomes and mammalian cells and identifies several steps that could be targets for the development of parasite-specific therapeutic agents. (C) 1999 Elsevier Science B.V. All rights reserved.",

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T1 - The GPI biosynthetic pathway as a therapeutic target for African sleeping sickness

AU - Ferguson, Michael A. J.

AU - Brimacombe, John S.

AU - Brown, Jillian R.

AU - Crossman, Arthur

AU - Dix, Alexander

AU - Field, Robert A.

AU - Guther, M. Lucia S.

AU - Milne, Kenneth G.

AU - Sharma, Deepak K.

AU - Smith, Terry K.

PY - 1999

Y1 - 1999

N2 - African sleeping sickness is a debilitating and often fatal disease caused by tsetse fly transmitted African trypanosomes. These extracellular protozoan parasites survive in the human bloodstream by virtue of a dense cell surface coat made of variant surface glycoprotein. The parasites have a repertoire of several hundred immunologically distinct variant surface glycoproteins and they evade the host immune response by antigenic variation. All variant surface glycoproteins are anchored to the plasma membrane via glycosylphosphatidylinositol membrane anchors and compounds that inhibit the assembly or transfer of these anchors could have trypanocidal potential. This article compares glycosylphosphatidylinositol biosynthesis in African trypanosomes and mammalian cells and identifies several steps that could be targets for the development of parasite-specific therapeutic agents. (C) 1999 Elsevier Science B.V. All rights reserved.

AB - African sleeping sickness is a debilitating and often fatal disease caused by tsetse fly transmitted African trypanosomes. These extracellular protozoan parasites survive in the human bloodstream by virtue of a dense cell surface coat made of variant surface glycoprotein. The parasites have a repertoire of several hundred immunologically distinct variant surface glycoproteins and they evade the host immune response by antigenic variation. All variant surface glycoproteins are anchored to the plasma membrane via glycosylphosphatidylinositol membrane anchors and compounds that inhibit the assembly or transfer of these anchors could have trypanocidal potential. This article compares glycosylphosphatidylinositol biosynthesis in African trypanosomes and mammalian cells and identifies several steps that could be targets for the development of parasite-specific therapeutic agents. (C) 1999 Elsevier Science B.V. All rights reserved.

U2 - 10.1016/S0925-4439(99)00058-7

DO - 10.1016/S0925-4439(99)00058-7

M3 - Article

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VL - 1455

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JO - BBA - Molecular Basis of Disease

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The GPI biosynthetic pathway as a therapeutic target for African sleeping sickness

Abstract

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