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Identification of the Bacterial Biosynthetic Gene Clusters of the Oral Microbiome Illuminates the Unexplored Social Language of Bacteria during Health and Disease
Aleti, Gajender ; Baker, Jonathon L. ; Tang, Xiaoyu ; Alvarez, Ruth ; Dinis, Márcia ; Tran, Nini C. ; Melnik, Alexey V. ; Zhong, Cuncong ; Ernst, Madeleine ; Dorrestein, Pieter C. ... show 1 more
Aleti, Gajender
Baker, Jonathon L.
Tang, Xiaoyu
Alvarez, Ruth
Dinis, Márcia
Tran, Nini C.
Melnik, Alexey V.
Zhong, Cuncong
Ernst, Madeleine
Dorrestein, Pieter C.
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Abstract
Small molecules are the primary communication media of the microbial world. Recent bioinformatic studies, exploring the biosynthetic gene clusters (BGCs) which produce many small molecules, have highlighted the incredible biochemical potential of the signaling molecules encoded by the human microbiome. Thus far, most research efforts have focused on understanding the social language of the gut microbiome, leaving crucial signaling molecules produced by oral bacteria and their connection to health versus disease in need of investigation. In this study, a total of 4,915 BGCs were identified across 461 genomes representing a broad taxonomic diversity of oral bacteria. Sequence similarity networking provided a putative product class for more than 100 unclassified novel BGCs. The newly identified BGCs were cross-referenced against 254 metagenomes and metatranscriptomes derived from individuals either with good oral health or with dental caries or periodontitis. This analysis revealed 2,473 BGCs, which were differentially represented across the oral microbiomes associated with health versus disease. Coabundance network analysis identified numerous inverse correlations between BGCs and specific oral taxa. These correlations were present in healthy individuals but greatly reduced in individuals with dental caries, which may suggest a defect in colonization resistance. Finally, corroborating mass spectrometry identified several compounds with homology to products of the predicted BGC classes. Together, these findings greatly expand the number of known biosynthetic pathways present in the oral microbiome and provide an atlas for experimental characterization of these abundant, yet poorly understood, molecules and socio-chemical relationships, which impact the development of caries and periodontitis, two of the world’s most common chronic diseases.
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This work is licensed under a Creative Commons Attribution 4.0 International License.
Date
2019-04-16
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Publisher
American Society for Microbiology
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Keywords
Biosynthetic gene clusters, Caries, Genome mining, Oral microbiome, Periodontitis, Small molecules
Citation
Aleti G, Baker JL, Tang X, Alvarez R, Dinis M, Tran NC, Melnik AV, Zhong C, Ernst M, Dorrestein PC, Edlund A. 2019. Identification of the bacterial biosynthetic gene clusters of the oral microbiome illuminates the unexplored social language of bacteria during health and disease. mBio 10:e00321-19. https://doi.org/10.1128/mBio.00321-19.