Biology subjects

Watson, A. R.

Publications and source records attributed to Watson, A. R..

5 recordsLinked to original sources

bioRxiv2024

Genomic Analyses Suggest No Risk of Vancomycin Resistance Transfer by Strain VE202-06

In 2016, the US Food and Drug Administration published guidance for the early development of live biotherapeutic products (LBPs)1. Of particular importance is the characterization of LBP strains and the potential transfer of antimicrobial resistance (AMR) genes to relevant microbial organisms in the recipients microbiota. Van der Lelie et al2, make unsupported claims that the LBP strain VE202-06 encodes a transferable vancomycin resistance element. Here we provide our analysis of the potential transfer of AMR by strain VE202-06. These data indicate that strain VE202-06 has no risk of transferring AMR to relevant microbial organisms.

genomics↗

bioRxiv2023

Microbes with higher metabolic independence are enriched in human gut microbiomes under stress

A wide variety of human diseases are associated with loss of microbial diversity in the human gut, inspiring a great interest in the diagnostic or therapeutic potential of the microbiota. However, the ecological forces that drive diversity reduction in disease states remain unclear, rendering it difficult to ascertain the role of the microbiota in disease emergence or severity. One hypothesis to explain this phenomenon is that microbial diversity is diminished as disease states select for microbial populations that are more fit to survive environmental stress caused by inflammation or other host factors. Here, we tested this hypothesis on a large scale, by developing a software framework to quantify the enrichment of microbial metabolisms in complex metagenomes as a function of microbial diversity. We applied this framework to over 400 gut metagenomes from individuals who are healthy or diagnosed with inflammatory bowel disease (IBD). We found that high metabolic independence (HMI) is a distinguishing characteristic of microbial communities associated with individuals diagnosed with IBD. A classifier we trained using the normalized copy numbers of 33 HMI-associated metabolic modules not only distinguished states of health versus IBD, but also tracked the recovery of the gut microbiome following antibiotic treatment, suggesting that HMI is a hallmark of microbial communities in stressed gut environments.

microbiology↗

bioRxiv2021

Adaptive ecological processes and metabolic independence drive microbial colonization and resilience in the human gut

Changes in microbial community composition as a function of human health and disease states have sparked remarkable interest in the human gut microbiome. However, establishing reproducible insights into the determinants of microbial succession in disease has been a formidable challenge. Here we use fecal microbiota transplantation (FMT) as an in natura experimental model to investigate the association between metabolic independence and resilience in stressed gut environments. Our genome-resolved metagenomics survey suggests that FMT serves as an environmental filter that favors populations with higher metabolic independence, the genomes of which encode complete metabolic modules to synthesize critical metabolites, including amino acids, nucleotides, and vitamins. Interestingly, we observe higher completion of the same biosynthetic pathways in microbes enriched in IBD patients. These observations suggest a general mechanism that underlies changes in diversity in perturbed gut environments, and reveal taxon-independent markers of dysbiosis that may explain why widespread yet typically low abundance members of healthy gut microbiomes can dominate under inflammatory conditions without any causal association with disease.

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↗

bioRxiv2019

The Tug1 Locus is Essential for Male Fertility

BackgroundSeveral long noncoding RNAs (lncRNAs) have been shown to function as central components of molecular machines that play fundamental roles in biology. While the number of annotated lncRNAs in mammalian genomes has greatly expanded, their functions remain largely uncharacterized. This is compounded by the fact that identifying lncRNA loci that have robust and reproducible phenotypes when mutated has been a challenge. ResultsWe previously generated a cohort of 20 lncRNA loci knockout mice. Here, we extend our initial study and provide a more detailed analysis of the highly conserved lncRNA locus, Taurine Upregulated Gene 1 (Tug1). We report that Tug1 knockout male mice are sterile with complete penetrance due to a low sperm count and abnormal sperm morphology. Having identified a lncRNA loci with a robust phenotype, we wanted to determine which, if any, potential elements contained in the Tug1 genomic region (DNA, RNA, protein, or the act of transcription) have activity. Using engineered mouse models and cell-based assays, we provide evidence that the Tug1 locus harbors three distinct regulatory activities - two noncoding and one coding: (i) a cis DNA repressor that regulates many neighboring genes, (ii) a lncRNA that can regulate genes by a trans-based function, and finally (iii) Tug1 encodes an evolutionary conserved peptide that when overexpressed impacts mitochondrial membrane potential. ConclusionsOur results reveal an essential role for the Tug1 locus in male fertility and uncover three distinct regulatory activities in the Tug1 locus, thus highlighting the complexity present at lncRNA loci.

genomics↗