Biology subjects

Dewhirst, F.

Publications and source records attributed to Dewhirst, F..

4 recordsLinked to original sources

bioRxiv2026

Site-specialization of human oral Porphyromonas species

Site-specificity within the human oral cavity reflects adaptation mechanisms such as genome divergence and metabolic specialization. Members of the genus Porphyromonas are distributed across oral sites in health and disease, yet the specific distribution of taxa and the functional basis of their site-specificity remain poorly understood. We analyzed 1,242 metagenomes from nine oral sites in healthy individuals and 24 subgingival plaque samples from individuals with periodontitis. Competitive mapping to a dereplicated genus-level pangenome of 84 reference genomes, combined with phylogenomic, gene-level detection, and functional profiling, revealed distinct site-specific distribution patterns, ecotype differentiation, and metabolic specialization across Porphyromonas taxa. Porphyromonas pasteri was the most abundant and widespread taxon in healthy subjects, comprising two ecotypes--one mucosal, one plaque-associated. Porphyromonas gingivalis was rare in healthy subjects but present in periodontal disease, although detected in only half of periodontitis samples. P. gingivalis exhibited the broadest metabolic repertoire, suggestive of a survival strategy adaptive to disparate conditions. In contrast, Porphyromonas catoniae, restricted to healthy dental plaque, lacked biosynthetic pathways for cobalamin, biotin, and serine, implying nutritional dependency on other taxa or the host. Porphyromonas endodontalis, detected in subgingival plaque across both health and disease, also lacked several metabolic pathways. A 44 kb conjugative element identified in P. gingivalis was detected across healthy and periodontitis subgingival plaque microbiomes independently of the P. gingivalis chromosome, indicating horizontal transfer. These findings reveal genomic divergence and complex metabolic specialization among Porphyromonas taxa, refining our understanding of their role in the ecological structure of the human oral microbiome. ImportanceMicrobial specialization within host-associated ecosystems is a key driver of community structure and function. The human oral cavity, with its spatially structured and ecologically diverse niches, offers a powerful model for studying these patterns. Our findings reveal that Porphyromonas taxa are largely restricted to specific oral sites, with Porphyromonas pasteri emerging as the most abundant and ecologically versatile member of the genus, and that large mobile elements shape genomic diversity across oral taxa. This work advances our understanding of microbial biogeography and highlights the ecological and metabolic significance of Porphyromonas taxa within the complex oral community.

microbiology↗

bioRxiv2020

Functional and genetic markers of niche partitioning among enigmatic members of the human oral microbiome

Microbial residents of the human oral cavity have long been a major focus of microbiology due to their influence on host health and their intriguing patterns of site specificity amidst the lack of dispersal limitation. Yet, the determinants of niche partitioning in this habitat are yet to be fully understood, especially among the taxa that belong to recently discovered branches of microbial life. Here we assembled metagenomes from daily tongue and dental plaque samples from multiple individuals and reconstructed 790 non-redundant genomes, 43 of which resolved to TM7 that formed six monophyletic clades distinctly associated either with plaque or with tongue. Both pangenomic and phylogenomic analyses grouped tongue-specific TM7 clades with other host-associated TM7 genomes. In contrast, plaque-specific TM7 grouped together with environmental TM7 genomes. Besides offering deeper insights into the ecology, evolution, and the mobilome of the cryptic members of the oral microbiome, our study reveals an intriguing resemblance between dental plaque and non-host environments indicated by the TM7 evolution, suggesting that plaque may have served as a stepping stone for environmental microbes to adapt to host environments for some clades of human associated microbes. Additionally, we report that prophages are widespread amongst oral-associated TM7, while absent from environmental TM7, suggesting that prophages may have played a role in adaptation of TM7 to the host environment.

microbiology↗

bioRxiv2018

Quantifying biosynthetic network robustness across the human oral microbiome

Metabolic interactions, such as cross-feeding, play a prominent role in microbial communitystructure. For example, they may underlie the ubiquity of uncultivated microorganisms. We investigated this phenomenon in the human oral microbiome, by analyzing microbial metabolic networks derived from sequenced genomes. Specifically, we devised a probabilistic biosynthetic network robustness metric that describes the chance that an organism could produce a given metabolite, and used it to assemble a comprehensive atlas of biosynthetic capabilities for 88 metabolites across 456 human oral microbiome strains. A cluster of organisms characterized by reduced biosynthetic capabilities stood out within this atlas. This cluster included several uncultivated taxa and three recently co-cultured Saccharibacteria (TM7) phylum species. Comparison across strains also allowed us to systematically identify specific putative metabolic interdependences between organisms. Our method, which provides a new way of converting annotated genomes into metabolic predictions, is easily extendible to other microbial communities and metabolic products.

systems biology↗

bioRxiv2018

SyngenicDNA: stealth-based evasion of restriction-modification barriers during bacterial genetic engineering

Restriction-modification (RM) systems hinder the use of genetic approaches in the vast majority of bacteria. Here, we describe a systematic approach to adapt genetic tools for use in bacteria that are genetically intractable or poorly tractable owing to active RM defenses. In this process, we determine the genome and methylome of a bacterial strain and use this information to define the bacteriums RM target motifs. We then synonymously eliminate RM targets from the nucleotide sequence of a genetic tool in silico, synthesize an RM-silent SyngenicDNA tool and propagate the tool as novel minicircle plasmids, termed SyMPL tools, before transformation. Using SyngenicDNA and SyMPL tools, we achieved a profound, >100,000- fold, improvement in the transformation of a clinically relevant USA300 strain of Staphylococcus aureus demonstrating the efficacy of these approaches for evading RM systems. The SyngenicDNA and SyMPL approaches are effective, flexible, and should be broadly applicable in microbial genetics. We expect these will facilitate a new era of microbial genetics free of the restraints of restriction-modification barriers.

microbiology↗