Identification of Trypanosome Proteins in Plasma from African Sleeping Sickness Patients Infected with T. b. rhodesiense

Control of human African sleeping sickness, caused by subspecies of the protozoan parasite Trypanosoma brucei, is based on preventing transmission by elimination of the tsetse vector and by active diagnostic screening and treatment of infected patients. To identify trypanosome proteins that have pot...

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Main Authors: Eyford, Brett A., Ahmad, Rushdy, Enyaru, John C., Pearson, Terry W., Carr, Steven A
Other Authors: Koch Institute for Integrative Cancer Research at MIT
Format: Article
Language:en_US
Published: Public Library of Science 2013
Online Access:http://hdl.handle.net/1721.1/81220
https://orcid.org/0000-0002-7203-4299
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author Eyford, Brett A.
Ahmad, Rushdy
Enyaru, John C.
Pearson, Terry W.
Carr, Steven A
author2 Koch Institute for Integrative Cancer Research at MIT
author_facet Koch Institute for Integrative Cancer Research at MIT
Eyford, Brett A.
Ahmad, Rushdy
Enyaru, John C.
Pearson, Terry W.
Carr, Steven A
author_sort Eyford, Brett A.
collection MIT
description Control of human African sleeping sickness, caused by subspecies of the protozoan parasite Trypanosoma brucei, is based on preventing transmission by elimination of the tsetse vector and by active diagnostic screening and treatment of infected patients. To identify trypanosome proteins that have potential as biomarkers for detection and monitoring of African sleeping sickness, we have used a ‘deep-mining” proteomics approach to identify trypanosome proteins in human plasma. Abundant human plasma proteins were removed by immunodepletion. Depleted plasma samples were then digested to peptides with trypsin, fractionated by basic reversed phase and each fraction analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). This sample processing and analysis method enabled identification of low levels of trypanosome proteins in pooled plasma from late stage sleeping sickness patients infected with Trypanosoma brucei rhodesiense. A total of 254 trypanosome proteins were confidently identified. Many of the parasite proteins identified were of unknown function, although metabolic enzymes, chaperones, proteases and ubiquitin-related/acting proteins were found. This approach to the identification of conserved, soluble trypanosome proteins in human plasma offers a possible route to improved disease diagnosis and monitoring, since these molecules are potential biomarkers for the development of a new generation of antigen-detection assays. The combined immuno-depletion/mass spectrometric approach can be applied to a variety of infectious diseases for unbiased biomarker identification.
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spelling mit-1721.1/812202022-09-26T12:07:25Z Identification of Trypanosome Proteins in Plasma from African Sleeping Sickness Patients Infected with T. b. rhodesiense Eyford, Brett A. Ahmad, Rushdy Enyaru, John C. Pearson, Terry W. Carr, Steven A Koch Institute for Integrative Cancer Research at MIT Carr, Steven A. Control of human African sleeping sickness, caused by subspecies of the protozoan parasite Trypanosoma brucei, is based on preventing transmission by elimination of the tsetse vector and by active diagnostic screening and treatment of infected patients. To identify trypanosome proteins that have potential as biomarkers for detection and monitoring of African sleeping sickness, we have used a ‘deep-mining” proteomics approach to identify trypanosome proteins in human plasma. Abundant human plasma proteins were removed by immunodepletion. Depleted plasma samples were then digested to peptides with trypsin, fractionated by basic reversed phase and each fraction analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). This sample processing and analysis method enabled identification of low levels of trypanosome proteins in pooled plasma from late stage sleeping sickness patients infected with Trypanosoma brucei rhodesiense. A total of 254 trypanosome proteins were confidently identified. Many of the parasite proteins identified were of unknown function, although metabolic enzymes, chaperones, proteases and ubiquitin-related/acting proteins were found. This approach to the identification of conserved, soluble trypanosome proteins in human plasma offers a possible route to improved disease diagnosis and monitoring, since these molecules are potential biomarkers for the development of a new generation of antigen-detection assays. The combined immuno-depletion/mass spectrometric approach can be applied to a variety of infectious diseases for unbiased biomarker identification. 2013-09-27T16:28:28Z 2013-09-27T16:28:28Z 2013-08 2013-02 Article http://purl.org/eprint/type/JournalArticle 1932-6203 http://hdl.handle.net/1721.1/81220 Eyford, Brett A., Rushdy Ahmad, John C. Enyaru, Steven A. Carr, and Terry W. Pearson. “Identification of Trypanosome Proteins in Plasma from African Sleeping Sickness Patients Infected with T. b. rhodesiense.” Edited by Joy Sturtevant. PLoS ONE 8, no. 8 (August 8, 2013): e71463. https://orcid.org/0000-0002-7203-4299 en_US http://dx.doi.org/10.1371/journal.pone.0071463 PLoS ONE Creative Commons Attribution http://creativecommons.org/licenses/by/2.5/ application/pdf Public Library of Science PLoS
spellingShingle Eyford, Brett A.
Ahmad, Rushdy
Enyaru, John C.
Pearson, Terry W.
Carr, Steven A
Identification of Trypanosome Proteins in Plasma from African Sleeping Sickness Patients Infected with T. b. rhodesiense
title Identification of Trypanosome Proteins in Plasma from African Sleeping Sickness Patients Infected with T. b. rhodesiense
title_full Identification of Trypanosome Proteins in Plasma from African Sleeping Sickness Patients Infected with T. b. rhodesiense
title_fullStr Identification of Trypanosome Proteins in Plasma from African Sleeping Sickness Patients Infected with T. b. rhodesiense
title_full_unstemmed Identification of Trypanosome Proteins in Plasma from African Sleeping Sickness Patients Infected with T. b. rhodesiense
title_short Identification of Trypanosome Proteins in Plasma from African Sleeping Sickness Patients Infected with T. b. rhodesiense
title_sort identification of trypanosome proteins in plasma from african sleeping sickness patients infected with t b rhodesiense
url http://hdl.handle.net/1721.1/81220
https://orcid.org/0000-0002-7203-4299
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