Identification of the bacterial biosynthetic gene clusters of the oral microbiome illuminates the unexplored social language of bacteria during health and disease
Jonathon L Baker,
Nini C Tran,
Alexey V. Melnik,
Pieter C. Dorrestein,
Posted 02 Oct 2018
bioRxiv DOI: 10.1101/431510 (published DOI: 10.1128/mBio.00321-19)
Posted 02 Oct 2018
Small molecules are the primary communication media of the microbial world. Recent bioinformatics 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 over 100 unclassified novel BGCs. The newly identified BGCs were cross-referenced against 254 metagenomes and metatranscriptomes derived from individuals with either good oral health, dental caries, or periodontitis. This analysis revealed 2,473 BGCs, which were differentially represented across the oral microbiomes associated with health versus disease. Co-abundance network analysis identified numerous inverse correlations between BGCs and specific oral taxa. These correlations were present in health, but greatly reduced in 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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