Biology subjects

Stares, M. D.

Publications and source records attributed to Stares, M. D..

3 recordsLinked to original sources

bioRxiv2022

In vitro demonstration of broad host range mobile genetic elements transferring antibiotic resistance from the human microbiome

Mobile genetic elements (MGEs) carrying antibiotic resistance genes (ARGs) disseminate ARGs when they mobilise into new bacterial hosts. To investigate the scale of such horizontal gene transfer (HGT) events between human gut commensals and enteropathogens for the first time, we compared 1354 cultured commensal strains (540 species) to 45,403 enteropathogen strains (12 species) and found 64,188 MGE-mediated ARG transfer events between the two groups using established methods. Among the 5931 MGEs involved, we found 15 broad host range elements predicted to have crossed different bacterial phyla while also occurring in animal and environmental microbiomes. We experimentally demonstrated that predicted broad host range MGEs can mobilise from commensals Dorea longicatena and Hungatella hathewayi to enteropathogens Klebsiella oxytoca, crossing phyla simultaneously. Our work establishes the MGE-mediated ARG dissemination network between human gut commensals and enteropathogens and highlights novel broad host range MGEs as targets for future ARG dissemination management.

genomics↗

bioRxiv2021

Functional and taxonomic comparison of mouse and human gut microbiotas using extensive culturing and metagenomics

Mouse models are essential for biomedical science and drug discovery, yet it is not known how the bacteria in the mouse microbiota - important determinants of phenotypes of health and disease -affect their relevance to human disease. To interrogate the taxonomic and functional differences between the human and mouse gut microbiotas, we developed the Mouse Microbial Genome Collection (MMGC), a compilation of 276 genomes from cultured isolates and 45,218 metagenome-assembled genomes (MAGs) from 1,960 publicly available mouse metagenomes. The MMGC reveals that while only 2.65% of bacterial species are shared between mouse and human, over 80% of annotatable functions are present in both microbiomes. Using drug metabolism and butyrate synthesis as examples, we illustrate that although the species harbouring these key functions can differ between hosts, the MMGC enables identification of functionally equivalent taxa in the mouse and human microbiotas. The MMGC thereby facilitates the informed use of mice in biomedical research by providing access to the conservation and taxonomic locations of bacterial functions of interest.

microbiology↗

bioRxiv2019

Distinct microbial and immune niches of the human colon

Gastrointestinal microbiota and immune cells interact closely and display regional specificity, but little is known about how these communities differ with location. Here, we simultaneously assess microbiota and single immune cells across the healthy, adult human colon, with paired characterisation of immune cells in the mesenteric lymph nodes, to delineate colonic immune niches at steady-state. We describe distinct T helper cell activation and migration profiles along the colon and characterise the transcriptional adaptation trajectory of T regulatory cells between lymphoid tissue and colon. Finally, we show increasing B cell accumulation, clonal expansion and mutational frequency from caecum to sigmoid colon, and link this to the increasing number of reactive bacterial species.

immunology↗