Genome mining unveils widespread natural product biosynthetic capacity in human oral microbe Streptococcus mutans

Liu, Liwei; Hao, Tingting; Xie, Zhoujie; Horsman, Geoff P.; Chen, Yihua

doi:10.1038/srep37479

Cited by 66 publications

(75 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Microbial natural products are still a rich source for novel lead compounds in the treatment of many diseases [4]. Among them, RiPPs are a rapidly growing class of natural products pervasive in all domains of life [42,43]. With the progress in genome sequencing and genome mining technology, research on the RiPPs has rapidly increased in the past few years [44].…”

Section: Discussionmentioning

confidence: 99%

Transcription-factor centric genome mining strategy for discovery of diverse unprecedented RiPP gene clusters

Zhu

Zheng

2018

Preprint

View full text Add to dashboard Cite

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a rapidly emerging group of natural products with diverse biological activity. Most of their biosynthetic mechanisms are well studied and the "genome mining" strategy based on homology has led to the unearthing of many new ribosomal natural products, including lantipeptides, lasso peptides, cyanobactins. These precursor-centric or biosynthetic protein-centric genome mining strategies have encouraged the discovery of RiPPs natural products. However, a limitation of these strategies is that the newly identified natural products are similar to the known products and novel families of RiPP pathways were overlooked by these strategies. In this work, we applied a transcription-factor centric genome mining strategy and diverse unique crosslinked RiPP gene clusters were predicted in several sequenced microorganisms. Our research could significantly expand the category of biosynthetic pathways of RiPP natural products and predict new resources for novel RiPPs. 2

show abstract

Section: Discussionmentioning

confidence: 99%

Transcription-factor centric genome mining strategy for discovery of diverse unprecedented RiPP gene clusters

Zhu

Zheng

2018

Preprint

View full text Add to dashboard Cite

show abstract

“…A single genome sequence for each bacterial species was included to circumvent the overrepresentation of BGCs from bacteria with a high number of genome representatives. Indeed, in a previous bioinformatics study of 169 S. mutans genomes, ~1,000 putative BGCs were identified, revealing an incredible potential to produce small molecules within one bacterial species (31). Therefore, it should be noted that the estimated BGC diversity reported here is likely underestimated.…”

Section: Resultsmentioning

confidence: 82%

Identification of the bacterial biosynthetic gene clusters of the oral microbiome illuminates the unexplored social language of bacteria during health and disease

Aleti

Baker

Tang

et al. 2018

Preprint

View full text Add to dashboard Cite

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. IMPORTANCEThe healthy oral microbiome is symbiotic with the human host, importantly providing colonization resistance against potential pathogens. Dental caries and periodontitis are two of the world's most common and costly chronic infectious diseases, and are caused by a localized dysbiosis of the oral microbiome. Bacterially produced small molecules, often encoded by BGCs, are the primary communication media of bacterial communities, and play a crucial, yet largely unknown, role in the transition from health to dysbiosis. This study provides a comprehensive mapping of the BGC repertoire of the human oral microbiome and identifies major differences in health compared to disease. Furthermore, BGC representation and expression is linked to the abundance of particular oral bacterial taxa in health versus dental caries and periodontitis. Overall, this study provides a significant insight into the chemical communication network of the healthy oral microbiome, and how it devolves in the case of two prominent diseases.KEY WORDS: oral microbiome, small-molecules, biosynthetic gene cluster, caries, periodontitis also implicated in system-wide health (21), stressing the urgent need to unravel the underlying factors that sh...

show abstract

“…Small molecules produced by BGCs are increasingly recognized to play major roles in species-species communication and interactions(10, 13), and a recent study predicted 355 strain-specific BGCs across 169 S. mutans genomes(20). Although the production of mutactins (a group of bacteriocins) has been recognized for contribution to the colonization and establishment of S. mutans in the dental biofilm(21), the roles of other genetically encoded small molecules in S. mutans is barely explored, with exception of the mutanobactins.…”

Section: Figurementioning

confidence: 99%

CariogenicStreptococcus mutansproduces strain-specific antibiotics that impair commensal colonization

Tang

Kudo

Baker

et al. 2019

Preprint

View full text Add to dashboard Cite

Streptococcus mutans is a common constituent of dental plaque and an etiologic agent of dental caries (tooth decay). Here we elucidate a biosynthetic pathway, encoded by globally distributed strains of S. mutans, which produces a series of bioactive small molecules including reutericyclin and two N-acyl tetramic acid analogues active against oral commensal bacteria. This pathway may provide S. mutans with a competitive advantage, promoting dysbiosis and caries pathogenesis.

show abstract

Genome mining unveils widespread natural product biosynthetic capacity in human oral microbe Streptococcus mutans

Cited by 66 publications

References 53 publications

Transcription-factor centric genome mining strategy for discovery of diverse unprecedented RiPP gene clusters

Transcription-factor centric genome mining strategy for discovery of diverse unprecedented RiPP gene clusters

Identification of the bacterial biosynthetic gene clusters of the oral microbiome illuminates the unexplored social language of bacteria during health and disease

CariogenicStreptococcus mutansproduces strain-specific antibiotics that impair commensal colonization

Contact Info

Product

Resources

About