Discovery of novel community-relevant small proteins in a simplified human intestinal microbiome
Abstract Background The intestinal microbiota plays a crucial role in protecting the host from pathogenic microbes, modulating immunity and regulating metabolic processes. We studied the simplified human intestinal microbiota (SIHUMIx) consisting of eight bacterial species with a particular focus on...
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BMC
2021-02-01
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Series: | Microbiome |
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Online Access: | https://doi.org/10.1186/s40168-020-00981-z |
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doaj-81a31d395603419c8db097384e4bbb01 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hannes Petruschke Christian Schori Sebastian Canzler Sarah Riesbeck Anja Poehlein Rolf Daniel Daniel Frei Tina Segessemann Johannes Zimmerman Georgios Marinos Christoph Kaleta Nico Jehmlich Christian H. Ahrens Martin von Bergen |
spellingShingle |
Hannes Petruschke Christian Schori Sebastian Canzler Sarah Riesbeck Anja Poehlein Rolf Daniel Daniel Frei Tina Segessemann Johannes Zimmerman Georgios Marinos Christoph Kaleta Nico Jehmlich Christian H. Ahrens Martin von Bergen Discovery of novel community-relevant small proteins in a simplified human intestinal microbiome Microbiome Small proteins (sProteins) SIHUMIx Human gut microbiome Proteogenomics iPtgxDB Metatranscriptomics |
author_facet |
Hannes Petruschke Christian Schori Sebastian Canzler Sarah Riesbeck Anja Poehlein Rolf Daniel Daniel Frei Tina Segessemann Johannes Zimmerman Georgios Marinos Christoph Kaleta Nico Jehmlich Christian H. Ahrens Martin von Bergen |
author_sort |
Hannes Petruschke |
title |
Discovery of novel community-relevant small proteins in a simplified human intestinal microbiome |
title_short |
Discovery of novel community-relevant small proteins in a simplified human intestinal microbiome |
title_full |
Discovery of novel community-relevant small proteins in a simplified human intestinal microbiome |
title_fullStr |
Discovery of novel community-relevant small proteins in a simplified human intestinal microbiome |
title_full_unstemmed |
Discovery of novel community-relevant small proteins in a simplified human intestinal microbiome |
title_sort |
discovery of novel community-relevant small proteins in a simplified human intestinal microbiome |
publisher |
BMC |
series |
Microbiome |
issn |
2049-2618 |
publishDate |
2021-02-01 |
description |
Abstract Background The intestinal microbiota plays a crucial role in protecting the host from pathogenic microbes, modulating immunity and regulating metabolic processes. We studied the simplified human intestinal microbiota (SIHUMIx) consisting of eight bacterial species with a particular focus on the discovery of novel small proteins with less than 100 amino acids (= sProteins), some of which may contribute to shape the simplified human intestinal microbiota. Although sProteins carry out a wide range of important functions, they are still often missed in genome annotations, and little is known about their structure and function in individual microbes and especially in microbial communities. Results We created a multi-species integrated proteogenomics search database (iPtgxDB) to enable a comprehensive identification of novel sProteins. Six of the eight SIHUMIx species, for which no complete genomes were available, were sequenced and de novo assembled. Several proteomics approaches including two earlier optimized sProtein enrichment strategies were applied to specifically increase the chances for novel sProtein discovery. The search of tandem mass spectrometry (MS/MS) data against the multi-species iPtgxDB enabled the identification of 31 novel sProteins, of which the expression of 30 was supported by metatranscriptomics data. Using synthetic peptides, we were able to validate the expression of 25 novel sProteins. The comparison of sProtein expression in each single strain versus a multi-species community cultivation showed that six of these sProteins were only identified in the SIHUMIx community indicating a potentially important role of sProteins in the organization of microbial communities. Two of these novel sProteins have a potential antimicrobial function. Metabolic modelling revealed that a third sProtein is located in a genomic region encoding several enzymes relevant for the community metabolism within SIHUMIx. Conclusions We outline an integrated experimental and bioinformatics workflow for the discovery of novel sProteins in a simplified intestinal model system that can be generically applied to other microbial communities. The further analysis of novel sProteins uniquely expressed in the SIHUMIx multi-species community is expected to enable new insights into the role of sProteins on the functionality of bacterial communities such as those of the human intestinal tract. Video abstract |
topic |
Small proteins (sProteins) SIHUMIx Human gut microbiome Proteogenomics iPtgxDB Metatranscriptomics |
url |
https://doi.org/10.1186/s40168-020-00981-z |
work_keys_str_mv |
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doaj-81a31d395603419c8db097384e4bbb012021-03-11T12:47:12ZengBMCMicrobiome2049-26182021-02-019111910.1186/s40168-020-00981-zDiscovery of novel community-relevant small proteins in a simplified human intestinal microbiomeHannes Petruschke0Christian Schori1Sebastian Canzler2Sarah Riesbeck3Anja Poehlein4Rolf Daniel5Daniel Frei6Tina Segessemann7Johannes Zimmerman8Georgios Marinos9Christoph Kaleta10Nico Jehmlich11Christian H. Ahrens12Martin von Bergen13Department of Molecular Systems Biology, Helmholtz-Centre for Environmental Research – UFZ GmbHAgroscope, Molecular Diagnostics, Genomics & Bioinformatics and SIB Swiss Institute of BioinformaticsDepartment of Molecular Systems Biology, Helmholtz-Centre for Environmental Research – UFZ GmbHDepartment of Molecular Systems Biology, Helmholtz-Centre for Environmental Research – UFZ GmbHInstitute of Microbiology and Genetics, Department of Genomic and Applied Microbiology, Georg-August University of GöttingenInstitute of Microbiology and Genetics, Department of Genomic and Applied Microbiology, Georg-August University of GöttingenAgroscope, Molecular Diagnostics, Genomics & Bioinformatics and SIB Swiss Institute of BioinformaticsAgroscope, Molecular Diagnostics, Genomics & Bioinformatics and SIB Swiss Institute of BioinformaticsResearch Group Medical Systems Biology, Institute for Experimental Medicine, Christian-Albrechts-University KielResearch Group Medical Systems Biology, Institute for Experimental Medicine, Christian-Albrechts-University KielResearch Group Medical Systems Biology, Institute for Experimental Medicine, Christian-Albrechts-University KielDepartment of Molecular Systems Biology, Helmholtz-Centre for Environmental Research – UFZ GmbHAgroscope, Molecular Diagnostics, Genomics & Bioinformatics and SIB Swiss Institute of BioinformaticsDepartment of Molecular Systems Biology, Helmholtz-Centre for Environmental Research – UFZ GmbHAbstract Background The intestinal microbiota plays a crucial role in protecting the host from pathogenic microbes, modulating immunity and regulating metabolic processes. We studied the simplified human intestinal microbiota (SIHUMIx) consisting of eight bacterial species with a particular focus on the discovery of novel small proteins with less than 100 amino acids (= sProteins), some of which may contribute to shape the simplified human intestinal microbiota. Although sProteins carry out a wide range of important functions, they are still often missed in genome annotations, and little is known about their structure and function in individual microbes and especially in microbial communities. Results We created a multi-species integrated proteogenomics search database (iPtgxDB) to enable a comprehensive identification of novel sProteins. Six of the eight SIHUMIx species, for which no complete genomes were available, were sequenced and de novo assembled. Several proteomics approaches including two earlier optimized sProtein enrichment strategies were applied to specifically increase the chances for novel sProtein discovery. The search of tandem mass spectrometry (MS/MS) data against the multi-species iPtgxDB enabled the identification of 31 novel sProteins, of which the expression of 30 was supported by metatranscriptomics data. Using synthetic peptides, we were able to validate the expression of 25 novel sProteins. The comparison of sProtein expression in each single strain versus a multi-species community cultivation showed that six of these sProteins were only identified in the SIHUMIx community indicating a potentially important role of sProteins in the organization of microbial communities. Two of these novel sProteins have a potential antimicrobial function. Metabolic modelling revealed that a third sProtein is located in a genomic region encoding several enzymes relevant for the community metabolism within SIHUMIx. Conclusions We outline an integrated experimental and bioinformatics workflow for the discovery of novel sProteins in a simplified intestinal model system that can be generically applied to other microbial communities. The further analysis of novel sProteins uniquely expressed in the SIHUMIx multi-species community is expected to enable new insights into the role of sProteins on the functionality of bacterial communities such as those of the human intestinal tract. Video abstracthttps://doi.org/10.1186/s40168-020-00981-zSmall proteins (sProteins)SIHUMIxHuman gut microbiomeProteogenomicsiPtgxDBMetatranscriptomics |