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Type VII Secretion Substrates of Pathogenic Mycobacteria Are Processed by a Surface Protease

Tuberculosis, one of the world’s most severe infectious diseases, is caused by Mycobacterium tuberculosis. A major weapon of this pathogen is a unique cell wall that protects the pathogen from eradication by the immune system. Mycobacteria have specialized secretion systems, e.g., type VII secretion...

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Autores principales: Burggraaf, Maroeska J., Speer, Alexander, Meijers, Aniek S., Ummels, Roy, van der Sar, Astrid M., Korotkov, Konstantin V., Bitter, Wilbert, Kuijl, Coenraad
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6819658/
https://www.ncbi.nlm.nih.gov/pubmed/31662454
http://dx.doi.org/10.1128/mBio.01951-19
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author Burggraaf, Maroeska J.
Speer, Alexander
Meijers, Aniek S.
Ummels, Roy
van der Sar, Astrid M.
Korotkov, Konstantin V.
Bitter, Wilbert
Kuijl, Coenraad
author_facet Burggraaf, Maroeska J.
Speer, Alexander
Meijers, Aniek S.
Ummels, Roy
van der Sar, Astrid M.
Korotkov, Konstantin V.
Bitter, Wilbert
Kuijl, Coenraad
author_sort Burggraaf, Maroeska J.
collection PubMed
description Tuberculosis, one of the world’s most severe infectious diseases, is caused by Mycobacterium tuberculosis. A major weapon of this pathogen is a unique cell wall that protects the pathogen from eradication by the immune system. Mycobacteria have specialized secretion systems, e.g., type VII secretion or ESX systems, to transport substrates across this cell wall. The largest group of proteins that are secreted by these ESX systems are the PE proteins. Previously, it was shown that the N-terminal PE domain of about 100 amino acids is required for secretion. Here, we describe the identification of an aspartic protease, designated PecA, that removes (part of) this PE domain at the cell surface. Nearly all of the observed PE_PGRS proteins are processed by PecA. Interestingly, the protease itself is also a secreted PE protein and subject to self-cleavage. Furthermore, a defect in surface processing has no effect on the activity of the PE lipase protein LipY but does seem to affect the functioning of other virulence factors, as a pecA mutant strain of Mycobacterium marinum shows moderate attenuation in zebrafish larvae. In conclusion, our results reveal the presence of a functional aspartic acid protease in M. marinum that cleaves LipY, itself as well as other members of the PE_PGRS family. Finally, mutants lacking PecA show growth attenuation in vivo, suggesting that PecA plays a role during infection.
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spelling pubmed-68196582019-11-07 Type VII Secretion Substrates of Pathogenic Mycobacteria Are Processed by a Surface Protease Burggraaf, Maroeska J. Speer, Alexander Meijers, Aniek S. Ummels, Roy van der Sar, Astrid M. Korotkov, Konstantin V. Bitter, Wilbert Kuijl, Coenraad mBio Research Article Tuberculosis, one of the world’s most severe infectious diseases, is caused by Mycobacterium tuberculosis. A major weapon of this pathogen is a unique cell wall that protects the pathogen from eradication by the immune system. Mycobacteria have specialized secretion systems, e.g., type VII secretion or ESX systems, to transport substrates across this cell wall. The largest group of proteins that are secreted by these ESX systems are the PE proteins. Previously, it was shown that the N-terminal PE domain of about 100 amino acids is required for secretion. Here, we describe the identification of an aspartic protease, designated PecA, that removes (part of) this PE domain at the cell surface. Nearly all of the observed PE_PGRS proteins are processed by PecA. Interestingly, the protease itself is also a secreted PE protein and subject to self-cleavage. Furthermore, a defect in surface processing has no effect on the activity of the PE lipase protein LipY but does seem to affect the functioning of other virulence factors, as a pecA mutant strain of Mycobacterium marinum shows moderate attenuation in zebrafish larvae. In conclusion, our results reveal the presence of a functional aspartic acid protease in M. marinum that cleaves LipY, itself as well as other members of the PE_PGRS family. Finally, mutants lacking PecA show growth attenuation in vivo, suggesting that PecA plays a role during infection. American Society for Microbiology 2019-10-29 /pmc/articles/PMC6819658/ /pubmed/31662454 http://dx.doi.org/10.1128/mBio.01951-19 Text en Copyright © 2019 Burggraaf et al. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Burggraaf, Maroeska J.
Speer, Alexander
Meijers, Aniek S.
Ummels, Roy
van der Sar, Astrid M.
Korotkov, Konstantin V.
Bitter, Wilbert
Kuijl, Coenraad
Type VII Secretion Substrates of Pathogenic Mycobacteria Are Processed by a Surface Protease
title Type VII Secretion Substrates of Pathogenic Mycobacteria Are Processed by a Surface Protease
title_full Type VII Secretion Substrates of Pathogenic Mycobacteria Are Processed by a Surface Protease
title_fullStr Type VII Secretion Substrates of Pathogenic Mycobacteria Are Processed by a Surface Protease
title_full_unstemmed Type VII Secretion Substrates of Pathogenic Mycobacteria Are Processed by a Surface Protease
title_short Type VII Secretion Substrates of Pathogenic Mycobacteria Are Processed by a Surface Protease
title_sort type vii secretion substrates of pathogenic mycobacteria are processed by a surface protease
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6819658/
https://www.ncbi.nlm.nih.gov/pubmed/31662454
http://dx.doi.org/10.1128/mBio.01951-19
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