Metabolic Fingerprints from the Human Oral Microbiome Reveal a Vast Knowledge Gap of Secreted Small Peptidic Molecules

ABSTRACT Recent research indicates that the human microbiota play key roles in maintaining health by providing essential nutrients, providing immune education, and preventing pathogen expansion. Processes underlying the transition from a healthy human microbiome to a disease-associated microbiome ar...

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Autores principales:	Anna Edlund, Neha Garg, Hosein Mohimani, Alexey Gurevich, Xuesong He, Wenyuan Shi, Pieter C. Dorrestein, Jeffrey S. McLean
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	Lactobacillus Streptococcus Veillonella biofilms oral microbiology peptidic small molecules Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/fef566cfc0a64d868ca2152dd4564eca
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spelling	oai:doaj.org-article:fef566cfc0a64d868ca2152dd4564eca2021-12-02T18:15:43ZMetabolic Fingerprints from the Human Oral Microbiome Reveal a Vast Knowledge Gap of Secreted Small Peptidic Molecules10.1128/mSystems.00058-172379-5077https://doaj.org/article/fef566cfc0a64d868ca2152dd4564eca2017-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSystems.00058-17https://doaj.org/toc/2379-5077ABSTRACT Recent research indicates that the human microbiota play key roles in maintaining health by providing essential nutrients, providing immune education, and preventing pathogen expansion. Processes underlying the transition from a healthy human microbiome to a disease-associated microbiome are poorly understood, partially because of the potential influences from a wide diversity of bacterium-derived compounds that are illy defined. Here, we present the analysis of peptidic small molecules (SMs) secreted from bacteria and viewed from a temporal perspective. Through comparative analysis of mass spectral profiles from a collection of cultured oral isolates and an established in vitro multispecies oral community, we found that the production of SMs both delineates a temporal expression pattern and allows discrimination between bacterial isolates at the species level. Importantly, the majority of the identified molecules were of unknown identity, and only ~2.2% could be annotated and classified. The catalogue of bacterially produced SMs we obtained in this study reveals an undiscovered molecular world for which compound isolation and ecosystem testing will facilitate a better understanding of their roles in human health and disease. IMPORTANCE Metabolomics is the ultimate tool for studies of microbial functions under any specific set of environmental conditions (D. S. Wishart, Nat Rev Drug Discov 45:473–484, 2016, https://doi.org/10.1038/nrd.2016.32 ). This is a great advance over studying genes alone, which only inform about metabolic potential. Approximately 25,000 compounds have been chemically characterized thus far; however, the richness of metabolites such as SMs has been estimated to be as high as 1 × 1030 in the biosphere (K. Garber, Nat Biotechnol 33:228–231, 2015, https://doi.org/10.1038/nbt.3161 ). Our classical, one-at-a-time activity-guided approach to compound identification continues to find the same known compounds and is also incredibly tedious, which represents a major bottleneck for global SM identification. These challenges have prompted new developments of databases and analysis tools that provide putative classifications of SMs by mass spectral alignments to already characterized tandem mass spectrometry spectra and databases containing structural information (e.g., PubChem and AntiMarin). In this study, we assessed secreted peptidic SMs (PSMs) from 27 oral bacterial isolates and a complex oral in vitro biofilm community of >100 species by using the Global Natural Products Social molecular Networking and the DEREPLICATOR infrastructures, which are methodologies that allow automated and putative annotation of PSMs. These approaches enabled the identification of an untapped resource of PSMs from oral bacteria showing species-unique patterns of secretion with putative matches to known bioactive compounds. Author Video: An author video summary of this article is available.Anna EdlundNeha GargHosein MohimaniAlexey GurevichXuesong HeWenyuan ShiPieter C. DorresteinJeffrey S. McLeanAmerican Society for MicrobiologyarticleLactobacillusStreptococcusVeillonellabiofilmsoral microbiologypeptidic small moleculesMicrobiologyQR1-502ENmSystems, Vol 2, Iss 4 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Lactobacillus Streptococcus Veillonella biofilms oral microbiology peptidic small molecules Microbiology QR1-502
spellingShingle	Lactobacillus Streptococcus Veillonella biofilms oral microbiology peptidic small molecules Microbiology QR1-502 Anna Edlund Neha Garg Hosein Mohimani Alexey Gurevich Xuesong He Wenyuan Shi Pieter C. Dorrestein Jeffrey S. McLean Metabolic Fingerprints from the Human Oral Microbiome Reveal a Vast Knowledge Gap of Secreted Small Peptidic Molecules
description	ABSTRACT Recent research indicates that the human microbiota play key roles in maintaining health by providing essential nutrients, providing immune education, and preventing pathogen expansion. Processes underlying the transition from a healthy human microbiome to a disease-associated microbiome are poorly understood, partially because of the potential influences from a wide diversity of bacterium-derived compounds that are illy defined. Here, we present the analysis of peptidic small molecules (SMs) secreted from bacteria and viewed from a temporal perspective. Through comparative analysis of mass spectral profiles from a collection of cultured oral isolates and an established in vitro multispecies oral community, we found that the production of SMs both delineates a temporal expression pattern and allows discrimination between bacterial isolates at the species level. Importantly, the majority of the identified molecules were of unknown identity, and only ~2.2% could be annotated and classified. The catalogue of bacterially produced SMs we obtained in this study reveals an undiscovered molecular world for which compound isolation and ecosystem testing will facilitate a better understanding of their roles in human health and disease. IMPORTANCE Metabolomics is the ultimate tool for studies of microbial functions under any specific set of environmental conditions (D. S. Wishart, Nat Rev Drug Discov 45:473–484, 2016, https://doi.org/10.1038/nrd.2016.32 ). This is a great advance over studying genes alone, which only inform about metabolic potential. Approximately 25,000 compounds have been chemically characterized thus far; however, the richness of metabolites such as SMs has been estimated to be as high as 1 × 1030 in the biosphere (K. Garber, Nat Biotechnol 33:228–231, 2015, https://doi.org/10.1038/nbt.3161 ). Our classical, one-at-a-time activity-guided approach to compound identification continues to find the same known compounds and is also incredibly tedious, which represents a major bottleneck for global SM identification. These challenges have prompted new developments of databases and analysis tools that provide putative classifications of SMs by mass spectral alignments to already characterized tandem mass spectrometry spectra and databases containing structural information (e.g., PubChem and AntiMarin). In this study, we assessed secreted peptidic SMs (PSMs) from 27 oral bacterial isolates and a complex oral in vitro biofilm community of >100 species by using the Global Natural Products Social molecular Networking and the DEREPLICATOR infrastructures, which are methodologies that allow automated and putative annotation of PSMs. These approaches enabled the identification of an untapped resource of PSMs from oral bacteria showing species-unique patterns of secretion with putative matches to known bioactive compounds. Author Video: An author video summary of this article is available.
format	article
author	Anna Edlund Neha Garg Hosein Mohimani Alexey Gurevich Xuesong He Wenyuan Shi Pieter C. Dorrestein Jeffrey S. McLean
author_facet	Anna Edlund Neha Garg Hosein Mohimani Alexey Gurevich Xuesong He Wenyuan Shi Pieter C. Dorrestein Jeffrey S. McLean
author_sort	Anna Edlund
title	Metabolic Fingerprints from the Human Oral Microbiome Reveal a Vast Knowledge Gap of Secreted Small Peptidic Molecules
title_short	Metabolic Fingerprints from the Human Oral Microbiome Reveal a Vast Knowledge Gap of Secreted Small Peptidic Molecules
title_full	Metabolic Fingerprints from the Human Oral Microbiome Reveal a Vast Knowledge Gap of Secreted Small Peptidic Molecules
title_fullStr	Metabolic Fingerprints from the Human Oral Microbiome Reveal a Vast Knowledge Gap of Secreted Small Peptidic Molecules
title_full_unstemmed	Metabolic Fingerprints from the Human Oral Microbiome Reveal a Vast Knowledge Gap of Secreted Small Peptidic Molecules
title_sort	metabolic fingerprints from the human oral microbiome reveal a vast knowledge gap of secreted small peptidic molecules
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/fef566cfc0a64d868ca2152dd4564eca
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Metabolic Fingerprints from the Human Oral Microbiome Reveal a Vast Knowledge Gap of Secreted Small Peptidic Molecules

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