Biology subjects

Draper, L. A.

Publications and source records attributed to Draper, L. A..

7 recordsLinked to original sources

bioRxiv2022

An IBD-associated pathobiont synergises with NSAID to promote colitis which is blocked by NLRP3 inflammasome and Caspase-8 inhibitors

Conflicting evidence exists on the association between consumption of non-steroidal anti-inflammatory drugs (NSAIDs) and symptomatic worsening of inflammatory bowel disease (IBD). We hypothesise that the heterogeneous prevalence of pathobionts [e.g., adherent-invasive Escherichia coli (AIEC)], might explain this inconsistent NSAIDs/IBD correlation. Using IL10 -/- mice, we show aggravation of colitis in AIEC-colonised animals fed NSAID. This is accompanied by activation of the NLRP3 inflammasome, Caspase-8, apoptosis and pyroptosis; features not seen in mice exposed to AIEC or NSAID alone, revealing an AIEC/NSAID synergistic effect. Inhibition of NLRP3 or Caspase-8 activity ameliorated colitis, with reduction in NLRP3 inflammasome activation, cell death markers and activated T-cells and macrophages, improved histology and increased abundance of Clostridium cluster XIVa species. Our findings provide mechanistic insights into how NSAID and an opportunistic gut-pathobiont can synergise to worsen IBD symptoms. Thus, targeting the NLRP3 inflammasome and Caspase-8 could be a potential therapeutic strategy in patients with NSAID-worsened inflammation.

immunology↗

bioRxiv2021

Alpha-synuclein alters the faecal viromes of rats in a gut-initiated model of Parkinson's disease

Parkinsons disease (PD) is a chronic neurological disorder associated with the misfolding of alpha-synuclein (-syn) into Lewy body aggregates within nerve cells that contribute to their neurodegeneration. Recent evidence suggests -syn aggregation may begin in the gut and travel to the brain along the vagus nerve, with microbes a potential trigger initiating the misfolding of -syn. However, changes in the gut virome in response to -syn alterations have not been investigated. In this study, we show longitudinal changes in the faecal virome of rats administered either monomeric or preformed fibrils (PFF) of -syn directly into their enteric nervous system. Differential changes in rat viromes were observed when comparing monomeric and PFF -syn. The virome {beta}-diversity changes after -syn treatment were compounded by the addition of LPS as an adjunct. Changes in the diversity of rat faecal viromes were observed after one month and did not resolve within the studys five month observational period. Overall, these results suggest that microbiome alterations associated with PD may, partially, be reactive to host -syn associated changes.

microbiology↗

bioRxiv2019

The human gut virome is highly diverse, stable and individual-specific

The human gut contains a vast array of viruses, mostly bacteriophages. The majority remain uncharacterised and their roles in shaping the gut microbiome and in impacting on human health remain poorly understood. Here we performed a longitudinal focused metagenomic study of faecal bacteriophage populations in healthy adults. Our results reveal high temporal stability and individual specificity of bacteriophage consortia which correlates with the bacterial microbiome. We report the existence of a stable, numerically predominant individual-specific persistent personal virome. Clustering of bacteriophage genomes and de novo taxonomic annotation identified several groups of crAss-like and Microviridae bacteriophages as the most stable colonizers of the human gut. CRISPR-based host prediction highlighted connections between these stable viral communities and highly predominant gut bacterial taxa such as Bacteroides, Prevotella and Faecalibacterium. This study provides insights into the structure of the human gut virome and serves as an important baseline for hypothesis-driven research.

microbiology↗

bioRxiv2019

Autochthonous faecal virome transplantation (FVT) reshapes the murine microbiome after antibiotic perturbation

BackgroundIt has become increasingly apparent that establishing and maintaining a complex and diverse gut microbiome is fundamental to human health. There are growing efforts to identify methods that can modulate and influence the microbiome, especially in individuals who due to disease or circumstance have experienced a disruption in their native microbiome. Faecal microbial transplantation (FMT) is one method that restores diversity to the microbiome of an individual by introducing microbes from a healthy donor. FMT introduces a complete microbiome into the recipient, including the bacteriome, archaeome, mycome and virome. In this study we investigated whether transplanting an autochthonous faecal virome consisting primarily of bacteriophages could impact a bacteriome disrupted by antibiotic treatment (Faecal Virome Transplantation; FVT).\n\nResultsFollowing disruption of the bacteriome by penicillin and streptomycin, test mice (n=8) received a bacteria free, faecal transplant, while Control mice (n=8) received a heated and nuclease treated control. The bacteriomes (as determined via 16S rRNA sequencing) of mice that received an FVT, in which bacteriophages predominate, separated from those of the Control mice as determined by principle co-ordinate analysis (PCoA), and contained differentially abundant taxa that reshaped the bacteriome profile such that it more closely resembled that of the pre-treatment mice. Similarly, metagenomic sequencing of the virome confirmed that the bacteriophages present in the gut of treatment and Control mice differed over time in both abundance and diversity, with transplanted phages seen to colonise the FVT mice.\n\nConclusionsAn autochthonous virome transplant impacts on the bacteriome and virome of mice following antibiotic treatment. The virome, consisting mainly of bacteriophages, reshapes the bacteriome such that it more closely resembles the pre-antibiotic state. To date, faecal transplants have largely focussed on transferring living microbes, but given that bacteriophage are inert biological entities incapable of colonising in the absence of a sensitive host they could form a viable alternative that may have fewer safety implications and that could be delivered as a robust formulation.

microbiology↗

bioRxiv2018

ΦCrAss001, a member of the most abundant bacteriophage family in the human gut, infects Bacteroides

{Phi}CrAss001, isolated from human faecal material, is the first member of the extensive crAssphage family to be grown in pure culture. The bacteriophage infects the human gut symbiont Bacteroides intestinalis, confirming in silico predictions of the likely host. Genome analysis demonstrated that the phage DNA is 102 kb in size, has an unusual genome organisation and does not possess any obvious genes for lysogeny. In addition, electron microscopy confirms that {varphi}crAss001 has a podovirus-like morphology. Despite the absence of lysogeny genes, {varphi}crAss001 replicates in a way that does not disrupt proliferation of the host bacterium and is able to maintain itself in continuous host culture.

microbiology↗

bioRxiv2018

Biology and taxonomy of crAss-like bacteriophages, the most abundant virus in the human gut

CrAssphage is yet to be cultured even though it represents the most abundant virus in the gut microbiota of humans. Recently, sequence based classification was performed on distantly related crAss-like phages from multiple environments, leading to the proposal of a familial level taxonomic group [Yutin N, et al. (2018) Discovery of an expansive bacteriophage family that includes the most abundant viruses from the human gut. Nat Microbiol 3(1):38-46]. Here, we assembled the metagenomic sequencing reads from 702 human faecal virome/phageome samples and obtained 98 complete circular crAss-like phage genomes and 145 contigs [≥]70kb. In silico comparative genomics and taxonomic analysis was performed, resulting in a classification scheme of crAss-like phages from human faecal microbiomes into 4 candidate subfamilies composed of 10 candidate genera. Moreover, laboratory analysis was performed on faecal samples from an individual harbouring 7 distinct crAss-like phages. We achieved propagation of crAss-like phages in ex vivo human faecal fermentations and visualised Podoviridae virions by electron microscopy. Furthermore, detection of a crAss-like phage capsid protein could be linked to metagenomic sequencing data confirming crAss-like phage structural annotations.\n\nSignificanceCrAssphage is the most abundant biological entity in the human gut, but it remains uncultured in the laboratory and its host(s) is unknown. CrAssphage was not identified in metagenomic studies for many years as its sequence is so different from anything present in databases. To this day, it can only be detected from sequences assembled from metagenomics or viromic datasets (crAss - cross Assembly). In this study, we identified 243 new crAss-like phages from human faecal metagenomic studies. Taxonomic analysis of these crAss-like phages highlighted their extensive diversity within the human microbiome. We also present the first propagation of crAssphage in faecal fermentations and provide the first electron micrographs of this extraordinary bacteriophage.

microbiology↗

bioRxiv2018

VIGA: a sensitive, precise and automatic de novo VIral Genome Annotator.

Viral (meta)genomics is a rapidly growing field of study that is hampered by an inability to annotate the majority of viral sequences; therefore, the development of new bioinformatic approaches is very important. Here, we present a new automatic de novo genome annotation pipeline, called VIGA, to annotate prokaryotic and eukaryotic viral sequences from (meta)genomic studies. VIGA was benchmarked on a database of known viral genomes and a viral metagenomics case study. VIGA generated the most accurate outputs according to the number of coding sequences and their coordinates, outputs also had a lower number of non-informative annotations compared to other programs.

bioinformatics↗