Biology subjects

Williams, R. B.

Publications and source records attributed to Williams, R. B..

4 recordsLinked to original sources

bioRxiv2025

Gut microbe-derived short-chain fatty acids regulate joint inflammation and activation of infiltrating and resident myeloid cells after alphavirus infection

Although oral antibiotics can predispose to joint inflammation, this phenomenon remains poorly understood. Here, we leverage mouse models of alphavirus-induced arthritis to investigate the roles of gut commensals, metabolites, and host immune mechanisms in promoting musculoskeletal inflammation. Mice treated with a short course of oral antibiotics exhibited worsened arthritis after chikungunya (CHIKV) or Mayaro virus infections. This phenotype was associated with loss of short chain fatty acids (SCFA), greater intestinal permeability, and activation of gut-associated immune cells, and required TLR4 signaling, MyD88 expression, monocytes, antigen-specific and bystander CD4+ T cells, and pro-inflammatory cytokines. Administration of exogenous SCFA or colonization of mice with bacterial species that generate SCFA mitigated CHIKV-induced joint inflammation. Single-cell RNA sequencing revealed that gut-derived SCFA ameliorate the inflammatory phenotype of synovial CD4+ T cells, infiltrating monocytes, and resident osteoclast-like cells. Thus, antibiotic-triggered gut dysbiosis exacerbates alphavirus arthritis by shaping the inflammatory profile of both infiltrating and resident immune cells in joint tissues.

immunology↗

bioRxiv2019

Evaluation of extraction solvents for untargeted metabolomics analysis of enrichment reactor cultures performing enhanced biological phosphorus removal (EBPR)

IntroductionThe extraction solvent mixtures were optimized for untargeted metabolomics analysis of microbial communities from two laboratory scale activated sludge reactors performing enhanced biological phosphorus removal (EBPR).\n\nObjectiveTo develop a robust and simple analytical protocol to analyse microbial metabolomics from EBPR bioreactors.\n\nMethodsExtra- and intra-cellular metabolites were extracted using five methods and analysed by ultraperformance liquid chromatography mass spectrometry (UPLC-MS).\n\nResultsThe optimal extraction method was biomass specific and methanol:water (1:1 v/v) and methanol:chloroform:water (2:2:1 v/v) were chosen, respectively, for each of the two different bioreactors.\n\nConclusionOur approach provides direct surveys of the metabolic state of PAO-enriched EBPR communities, showing that extraction methods should be carefully tailored to the microbial community under study

systems biology↗

bioRxiv2019

Annotated bacterial chromosomes from frame-shift-corrected long read metagenomic data

BackgroundShort-read sequencing technologies have long been the work-horse of microbiome analysis. Continuing technological advances are making the application of long-read sequencing to metagenomic samples increasingly feasible.\n\nResultsWe demonstrate that whole bacterial chromosomes can be obtained from a complex community, by application of MinION sequencing to a sample from an EBPR bio-reactor, producing 6Gb of sequence that assembles in to multiple closed bacterial chromosomes. We provide a simple pipeline for processing such data, which includes a new approach to correcting erroneous frame-shifts.\n\nConclusionsAdvances in long read sequencing technology and corresponding algorithms will allow the routine extraction of whole chromosomes from environmental samples, providing a more detailed picture of individual members of a microbiome.

bioinformatics↗

bioRxiv2018

Improving recovery of member genomes from enrichment reactor microbial communities using MinION--based long read metagenomics

New long read sequencing technologies offer huge potential for effective recovery of complete, closed genomes. While much progress has been made on cultured isolates, the ability of these methods to recover genomes of member taxa in complex microbial communities is less clear. Here we examine the ability of long read data to recover genomes from enrichment reactor metagenomes. Such modified communities offer a moderate level of complexity compared to the source communities and so are realistic, yet tractable, systems to use for this problem. We sampled an enrichment bioreactor designed to target anaerobic ammonium-oxidising bacteria (AnAOB) and sequenced genomic DNA using both short read (Illumina 301bp PE) and long read data (MinION Mk1B) from the same extraction aliquot. The community contained 23 members, of which 16 had genome bins defined from an assembly of the short read data. Two distinct AnAOB species from genus Candidatus Brocadia were present and had complete genomes, of which one was the most abundant member species in the community. We can recover a 4Mb genome, in 2 contigs, of long read assembled sequence that is unambiguously associated with the most abundant AnAOB member genome. We conclude that obtaining near closed, complete genomes of members of low-medium microbial communities using MinION long read sequence is feasible.

genomics↗