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Secretome characterization of clinical isolates from the Mycobacterium abscessus complex provides insight into antigenic differences
BACKGROUND: Mycobacterium abscessus (MAB) is a widely disseminated pathogenic non-tuberculous mycobacterium (NTM). Like with the M. tuberculosis complex (MTBC), excreted / secreted (ES) proteins play an essential role for its virulence and survival inside the host. Here, we used a robust bioinformat...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8152154/ https://www.ncbi.nlm.nih.gov/pubmed/34034663 http://dx.doi.org/10.1186/s12864-021-07670-7 |
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author | Cornejo-Granados, Fernanda Kohl, Thomas A. Sotomayor, Flor Vásquez Andres, Sönke Hernández-Pando, Rogelio Hurtado-Ramirez, Juan Manuel Utpatel, Christian Niemann, Stefan Maurer, Florian P. Ochoa-Leyva, Adrian |
author_facet | Cornejo-Granados, Fernanda Kohl, Thomas A. Sotomayor, Flor Vásquez Andres, Sönke Hernández-Pando, Rogelio Hurtado-Ramirez, Juan Manuel Utpatel, Christian Niemann, Stefan Maurer, Florian P. Ochoa-Leyva, Adrian |
author_sort | Cornejo-Granados, Fernanda |
collection | PubMed |
description | BACKGROUND: Mycobacterium abscessus (MAB) is a widely disseminated pathogenic non-tuberculous mycobacterium (NTM). Like with the M. tuberculosis complex (MTBC), excreted / secreted (ES) proteins play an essential role for its virulence and survival inside the host. Here, we used a robust bioinformatics pipeline to predict the secretome of the M. abscessus ATCC 19977 reference strain and 15 clinical isolates belonging to all three MAB subspecies, M. abscessus subsp. abscessus, M. abscessus subsp. bolletii, and M. abscessus subsp. massiliense. RESULTS: We found that ~ 18% of the proteins encoded in the MAB genomes were predicted as secreted and that the three MAB subspecies shared > 85% of the predicted secretomes. MAB isolates with a rough (R) colony morphotype showed larger predicted secretomes than isolates with a smooth (S) morphotype. Additionally, proteins exclusive to the secretomes of MAB R variants had higher antigenic densities than those exclusive to S variants, independent of the subspecies. For all investigated isolates, ES proteins had a significantly higher antigenic density than non-ES proteins. We identified 337 MAB ES proteins with homologues in previously investigated M. tuberculosis secretomes. Among these, 222 have previous experimental support of secretion, and some proteins showed homology with protein drug targets reported in the DrugBank database. The predicted MAB secretomes showed a higher abundance of proteins related to quorum-sensing and Mce domains as compared to MTBC indicating the importance of these pathways for MAB pathogenicity and virulence. Comparison of the predicted secretome of M. abscessus ATCC 19977 with the list of essential genes revealed that 99 secreted proteins corresponded to essential proteins required for in vitro growth. CONCLUSIONS: This study represents the first systematic prediction and in silico characterization of the MAB secretome. Our study demonstrates that bioinformatics strategies can help to broadly explore mycobacterial secretomes including those of clinical isolates and to tailor subsequent, complex and time-consuming experimental approaches accordingly. This approach can support systematic investigation exploring candidate proteins for new vaccines and diagnostic markers to distinguish between colonization and infection. All predicted secretomes were deposited in the Secret-AAR web-server (http://microbiomics.ibt.unam.mx/tools/aar/index.php). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12864-021-07670-7. |
format | Online Article Text |
id | pubmed-8152154 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-81521542021-05-26 Secretome characterization of clinical isolates from the Mycobacterium abscessus complex provides insight into antigenic differences Cornejo-Granados, Fernanda Kohl, Thomas A. Sotomayor, Flor Vásquez Andres, Sönke Hernández-Pando, Rogelio Hurtado-Ramirez, Juan Manuel Utpatel, Christian Niemann, Stefan Maurer, Florian P. Ochoa-Leyva, Adrian BMC Genomics Research BACKGROUND: Mycobacterium abscessus (MAB) is a widely disseminated pathogenic non-tuberculous mycobacterium (NTM). Like with the M. tuberculosis complex (MTBC), excreted / secreted (ES) proteins play an essential role for its virulence and survival inside the host. Here, we used a robust bioinformatics pipeline to predict the secretome of the M. abscessus ATCC 19977 reference strain and 15 clinical isolates belonging to all three MAB subspecies, M. abscessus subsp. abscessus, M. abscessus subsp. bolletii, and M. abscessus subsp. massiliense. RESULTS: We found that ~ 18% of the proteins encoded in the MAB genomes were predicted as secreted and that the three MAB subspecies shared > 85% of the predicted secretomes. MAB isolates with a rough (R) colony morphotype showed larger predicted secretomes than isolates with a smooth (S) morphotype. Additionally, proteins exclusive to the secretomes of MAB R variants had higher antigenic densities than those exclusive to S variants, independent of the subspecies. For all investigated isolates, ES proteins had a significantly higher antigenic density than non-ES proteins. We identified 337 MAB ES proteins with homologues in previously investigated M. tuberculosis secretomes. Among these, 222 have previous experimental support of secretion, and some proteins showed homology with protein drug targets reported in the DrugBank database. The predicted MAB secretomes showed a higher abundance of proteins related to quorum-sensing and Mce domains as compared to MTBC indicating the importance of these pathways for MAB pathogenicity and virulence. Comparison of the predicted secretome of M. abscessus ATCC 19977 with the list of essential genes revealed that 99 secreted proteins corresponded to essential proteins required for in vitro growth. CONCLUSIONS: This study represents the first systematic prediction and in silico characterization of the MAB secretome. Our study demonstrates that bioinformatics strategies can help to broadly explore mycobacterial secretomes including those of clinical isolates and to tailor subsequent, complex and time-consuming experimental approaches accordingly. This approach can support systematic investigation exploring candidate proteins for new vaccines and diagnostic markers to distinguish between colonization and infection. All predicted secretomes were deposited in the Secret-AAR web-server (http://microbiomics.ibt.unam.mx/tools/aar/index.php). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12864-021-07670-7. BioMed Central 2021-05-25 /pmc/articles/PMC8152154/ /pubmed/34034663 http://dx.doi.org/10.1186/s12864-021-07670-7 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Cornejo-Granados, Fernanda Kohl, Thomas A. Sotomayor, Flor Vásquez Andres, Sönke Hernández-Pando, Rogelio Hurtado-Ramirez, Juan Manuel Utpatel, Christian Niemann, Stefan Maurer, Florian P. Ochoa-Leyva, Adrian Secretome characterization of clinical isolates from the Mycobacterium abscessus complex provides insight into antigenic differences |
title | Secretome characterization of clinical isolates from the Mycobacterium abscessus complex provides insight into antigenic differences |
title_full | Secretome characterization of clinical isolates from the Mycobacterium abscessus complex provides insight into antigenic differences |
title_fullStr | Secretome characterization of clinical isolates from the Mycobacterium abscessus complex provides insight into antigenic differences |
title_full_unstemmed | Secretome characterization of clinical isolates from the Mycobacterium abscessus complex provides insight into antigenic differences |
title_short | Secretome characterization of clinical isolates from the Mycobacterium abscessus complex provides insight into antigenic differences |
title_sort | secretome characterization of clinical isolates from the mycobacterium abscessus complex provides insight into antigenic differences |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8152154/ https://www.ncbi.nlm.nih.gov/pubmed/34034663 http://dx.doi.org/10.1186/s12864-021-07670-7 |
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