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Cathepsin B Gene Disruption Induced Leishmania donovani Proteome Remodeling Implies Cathepsin B Role in Secretome Regulation

Leishmania cysteine proteases are potential vaccine candidates and drug targets. To study the role of cathepsin B cysteine protease, we have generated and characterized cathepsin B null mutant L. donovani parasites. L. donovani cathepsin B null mutants grow normally in culture, but they show signifi...

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Autores principales: Gerbaba, Teklu Kuru, Gedamu, Lashitew
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3828211/
https://www.ncbi.nlm.nih.gov/pubmed/24244582
http://dx.doi.org/10.1371/journal.pone.0079951
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author Gerbaba, Teklu Kuru
Gedamu, Lashitew
author_facet Gerbaba, Teklu Kuru
Gedamu, Lashitew
author_sort Gerbaba, Teklu Kuru
collection PubMed
description Leishmania cysteine proteases are potential vaccine candidates and drug targets. To study the role of cathepsin B cysteine protease, we have generated and characterized cathepsin B null mutant L. donovani parasites. L. donovani cathepsin B null mutants grow normally in culture, but they show significantly attenuated virulence inside macrophages. Quantitative proteome profiling of wild type and null mutant parasites indicates cathepsin B disruption induced remodeling of L. donovani proteome. We identified 83 modulated proteins, of which 65 are decreased and 18 are increased in the null mutant parasites, and 66% (55/83) of the modulated proteins are L. donovani secreted proteins. Proteins involved in oxidation-reduction (trypanothione reductase, peroxidoxins, tryparedoxin, cytochromes) and translation (ribosomal proteins) are among those decreased in the null mutant parasites, and most of these proteins belong to the same complex network of proteins. Our results imply virulence role of cathepsin B via regulation of Leishmania secreted proteins.
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spelling pubmed-38282112013-11-16 Cathepsin B Gene Disruption Induced Leishmania donovani Proteome Remodeling Implies Cathepsin B Role in Secretome Regulation Gerbaba, Teklu Kuru Gedamu, Lashitew PLoS One Research Article Leishmania cysteine proteases are potential vaccine candidates and drug targets. To study the role of cathepsin B cysteine protease, we have generated and characterized cathepsin B null mutant L. donovani parasites. L. donovani cathepsin B null mutants grow normally in culture, but they show significantly attenuated virulence inside macrophages. Quantitative proteome profiling of wild type and null mutant parasites indicates cathepsin B disruption induced remodeling of L. donovani proteome. We identified 83 modulated proteins, of which 65 are decreased and 18 are increased in the null mutant parasites, and 66% (55/83) of the modulated proteins are L. donovani secreted proteins. Proteins involved in oxidation-reduction (trypanothione reductase, peroxidoxins, tryparedoxin, cytochromes) and translation (ribosomal proteins) are among those decreased in the null mutant parasites, and most of these proteins belong to the same complex network of proteins. Our results imply virulence role of cathepsin B via regulation of Leishmania secreted proteins. Public Library of Science 2013-11-14 /pmc/articles/PMC3828211/ /pubmed/24244582 http://dx.doi.org/10.1371/journal.pone.0079951 Text en © 2013 Gerbaba, Gedamu http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Gerbaba, Teklu Kuru
Gedamu, Lashitew
Cathepsin B Gene Disruption Induced Leishmania donovani Proteome Remodeling Implies Cathepsin B Role in Secretome Regulation
title Cathepsin B Gene Disruption Induced Leishmania donovani Proteome Remodeling Implies Cathepsin B Role in Secretome Regulation
title_full Cathepsin B Gene Disruption Induced Leishmania donovani Proteome Remodeling Implies Cathepsin B Role in Secretome Regulation
title_fullStr Cathepsin B Gene Disruption Induced Leishmania donovani Proteome Remodeling Implies Cathepsin B Role in Secretome Regulation
title_full_unstemmed Cathepsin B Gene Disruption Induced Leishmania donovani Proteome Remodeling Implies Cathepsin B Role in Secretome Regulation
title_short Cathepsin B Gene Disruption Induced Leishmania donovani Proteome Remodeling Implies Cathepsin B Role in Secretome Regulation
title_sort cathepsin b gene disruption induced leishmania donovani proteome remodeling implies cathepsin b role in secretome regulation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3828211/
https://www.ncbi.nlm.nih.gov/pubmed/24244582
http://dx.doi.org/10.1371/journal.pone.0079951
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