Biology subjects

Dinsdale, E. A.

Publications and source records attributed to Dinsdale, E. A..

9 recordsLinked to original sources

bioRxiv2026

Functional redundancy and anaerobic metabolism characterize the skin microbiome of a critically endangered sawfish

Using shotgun metagenomics of largetooth sawfish (Pristis pristis) skin and paired pool water samples, we provide the first taxonomic and functional characterization of a sawfish skin microbiome and assess its ecological distinctiveness, assembly, and resilience relative to the surrounding water column. The skin microbiome was strongly host-associated and compositionally distinct, with lower taxonomic richness than the water column but dominated by Bacillota, particularly spore-forming Bacilli. Functional profiling revealed enrichment of genes associated with sporulation, dormancy, anaerobic metabolism, and peptide transport, consistent with adaptation to low-oxygen, low-flow pool conditions. In contrast, water-column microbiomes were more taxonomically diverse and enriched in phototrophic and polysaccharide-utilization pathways. Despite reduced taxonomic diversity, sawfish skin communities exhibited higher functional redundancy, with gene functions accumulating more rapidly per taxon. This pattern supports a host-filtered, lottery-like assembly process that produces taxonomically variable yet functionally conserved communities. The enrichment of dormancy and anaerobic pathways suggests the skin microbiome persists through periods of host quiescence and environmental stress while maintaining metabolic potential. Together, these results demonstrate that the sawfish skin supports a resilient, functionally robust microbiome distinct from ambient aquatic communities, highlighting the potential for integrating microbial functional data into conservation strategies for Critically Endangered vertebrates.

ecology↗

bioRxiv2024

Sphae: An automated toolkit for predicting phage therapy candidates from sequencing data

MotivationPhage therapy is a viable alternative for treating bacterial infections amidst the escalating threat of antimicrobial resistance. However, the therapeutic success of phage therapy depends on selecting safe and effective phage candidates. While experimental methods focus on isolating phages and determining their lifecycle and host range, comprehensive genomic screening is critical to identify markers that indicate potential risks, such as toxins, antimicrobial resistance, or temperate lifecycle traits. These analyses are often labor-intensive and time-consuming, limiting the rapid deployment of phage in clinical settings. ResultsWe developed Sphae, an automated bioinformatics pipeline designed to streamline therapeutic potential of a phage in under ten minutes. Using Snakemake workflow manager, Sphae integrates tools for quality control, assembly, genome assessment, and annotation tailored specifically for phage biology. Sphae automates the detection of key genomic markers, including virulence factors, antimicrobial resistance genes, and lysogeny indicators like integrase, recombinase, and transposase, which could preclude therapeutic use. Benchmarked on 65 phage sequences, 28 phage samples showed therapeutic potential, 8 failed during assembly due to low sequencing depth, 22 samples included prophage or virulent markers, and the remaining 23 samples included multiple phage genomes per sample. This workflow outputs a comprehensive report, enabling rapid assessment of phage safety and suitability for phage therapy under these criteria. Sphae is scalable, portable, facilitating efficient deployment across most high-performance computing (HPC) and cloud platforms, expediting the genomic evaluation process. AvailabilitySphae is source code and freely available at https://github.com/linsalrob/sphae, with installation supported on Conda, PyPi, Docker containers.

bioinformatics↗

bioRxiv2024

Elasmobranchs Exhibit Species-Specific Epidermal Microbiomes Guided by Denticle Topography

Elasmobranch epidermal microbiomes are species-specific, yet microbial assembly and retainment drivers are mainly unknown. The contribution of host-derived factors in recruiting an associated microbiome is essential for understanding host-microbe interactions. Here, we focus on the physical aspect of the host skin in structuring microbial communities. Each species of elasmobranch exhibits unique denticle morphology, and we investigate whether microbial communities and functional pathways are correlated with the morphological features or follow the phylogeny of the three species. We extracted and sequenced the DNA from the epidermal microbial communities of three captive shark species: Horn (Heterodontus francisci), Leopard (Triakis semifasciata), and Swell shark (Cephaloscyllium ventriosum) and use electron microscopy to measure the dermal denticle features of each species. Our results outline species-specific microbial communities, as microbiome compositions vary at the phyla level; C. ventriosum hosted a higher relative abundance of Pseudomonadota and Bacillota, while H. francisci were associated with a higher prevalence of Euryarchaeota and Aquificae, and Bacteroidota and Crenarchaeota were ubiquitous with T. semifasciata. Functional pathways performed by each species respective microbiome were species-specific metabolic. Microbial genes associated with aminosugars and electron-accepting reactions were correlated with the distance between dermal denticles, whereas desiccation stress genes were only present when the dermal denticle overlapped. Microbial genes associated with Pyrimidines, chemotaxis and virulence followed the phylogeny of the sharks. Several microbial genera display associations that resemble host evolutionary lineage, while others had linear relationships with interdenticle distance. Therefore, denticle morphology was a selective influence for some microbes and functions in the microbiome contributing to the phylosymbiosis. ImportanceMicrobial communities form species-specific relationships with vertebrate hosts, but the drivers of these relationships remain an outstanding question. We explore the relationship between a physical feature of the host and the microbial community. A distinguishing feature of the subclass Elasmobranchii (sharks, rays, and skates), is the presence of dermal denticles on the skin. These structures protrude through the epidermis providing increased swimming efficiency for the host and an artificial model skin affect microbial recruitment and establishment of cultured microbes but has not been tested on natural microbiomes. Here, we show some naturally occurring microbial genera and functional attributes were correlated with dermal denticle features, suggesting they are one, but not only contributing factor in microbiome structure on benthic sharks.

microbiology↗

bioRxiv2023

Bioenergetic mapping of 'healthy microbiomes' via compound processing potential imprinted in gut and soil metagenomes

Despite mounting evidence of their importance in human health and ecosystem functioning, the definition and measurement of healthy microbiomes remain unclear. More advanced knowledge exists on health associations for compounds used or produced by microbes. Environmental microbiome exposures (especially via soils) also help shape, and may supplement, the functional capacity of human microbiomes. Given the synchronous interaction between microbes, their feedstocks, and micro-environments, with functional genes facilitating chemical transformations, there exists an intriguing opportunity to examine microbiomes in terms of their capacity to process compounds relevant to human health. Here we integrate functional genomics and biochemistry frameworks to derive new quantitative measures of the potential for human gut and environmental soil metagenomes to process major compound classes (e.g., lipids, carbohydrates) and selected biomolecules (e.g., vitamins, short-chain fatty acids) linked to human health. Metagenome functional potential profile data were translated into a universal compound mapping landscape based on bioenergetic van Krevelen mapping of function-level meta-compounds and corresponding functional relative abundances, reflecting imprinted genetic capacity of microbiomes to metabolize an array of different compounds. We show that measures of compound processing potential associated with human health and disease (examining atherosclerotic cardiovascular disease, colorectal cancer, type 2 diabetes and anxious-depressive behavior case studies), and displayed seemingly predictable shifts along gradients of ecological disturbance in plant-soil ecosystems (three case studies). Ecosystem quality explained 60-92% of variation in soil metagenome compound processing potential measures in a post-mining restoration case study dataset. With growing knowledge of the varying proficiency of environmental microbiota to process human health associated compounds, we might design environmental interventions or nature prescriptions to modulate our exposures, thereby advancing microbiota-oriented approaches to human health. Compound processing potential offers a simplified, integrative approach for applying metagenomics in ongoing efforts to understand and quantify the role and linkages of microbiota in environmental- and human-health.

bioinformatics↗

bioRxiv2023

The Promise and Pitfalls of Prophages

Phages dominate every ecosystem on the planet. While virulent phages sculpt the microbiome by killing their bacterial hosts, temperate phages provide unique growth advantages to their hosts through lysogenic conversion. Many prophages benefit their host, and prophages are responsible for genotypic and phenotypic differences that separate individual microbial strains. However, the microbes also endure a cost to maintain those phages: additional DNA to replicate and proteins to transcribe and translate. We have never quantified those benefits and costs. Here, we analysed over two and a half million prophages from over half a million bacterial genome assemblies. Analysis of the whole dataset and a representative subset of taxonomically diverse bacterial genomes demonstrated that the normalised prophage density was uniform across all bacterial genomes above 2 Mbp. We identified a constant carrying capacity of phage DNA per bacterial DNA. We estimated that each prophage provides cellular services equivalent to approximately 2.4 % of the cells energy or 0.9 ATP per bp per hour. We demonstrate analytical, taxonomic, geographic, and temporal disparities in identifying prophages in bacterial genomes that provide novel targets for identifying new phages. We anticipate that the benefits bacteria accrue from the presence of prophages balance the energetics involved in supporting prophages. Furthermore, our data will provide a new framework for identifying phages in environmental datasets, diverse bacterial phyla, and from different locations.

bioinformatics↗

bioRxiv2023

Phables: from fragmented assemblies to high-quality bacteriophage genomes

MotivationMicrobial communities influence both human health and different environments. Viruses infecting bacteria, known as bacteriophages or phages, play a key role in modulating bacterial communities within environments. High-quality phage genome sequences are essential for advancing our understanding of phage biology, enabling comparative genomics studies, and developing phage-based diagnostic tools. Most available viral identification tools consider individual sequences to determine whether they are of viral origin. As a result of the challenges in viral assembly, fragmentation of genomes can occur, leading to the need for new approaches in viral identification. Therefore, the identification and characterisation of novel phages remain a challenge. ResultsWe introduce Phables, a new computational method to resolve phage genomes from fragmented viral metagenome assemblies. Phables identifies phage-like components in the assembly graph, models each component as a flow network, and uses graph algorithms and flow decomposition techniques to identify genomic paths. Experimental results of viral metagenomic samples obtained from different environments show that Phables recovers on average over 49% more high-quality phage genomes compared to existing viral identification tools. Furthermore, Phables can resolve variant phage genomes with over 99% average nucleotide identity, a distinction that existing tools are unable to make. Availability and ImplementationPhables is available on GitHub at https://github.com/Vini2/phables. Contactvijini.mallawaarachchi@flinders.edu.au

bioinformatics↗

bioRxiv2023

Novel crAssphage isolates exhibit conserved gene order and purifying selection of the host specificity protein

Bacteroides, the prominent bacteria in the human gut, play a crucial role in degrading complex polysaccharides. Their abundance is influenced by phages belonging to the Crassvirales order. Despite identifying over 600 Crassvirales genomes computationally, only few have been successfully isolated. Continued efforts in isolation of more Crassvirales genomes can provide insights into phage-host-evolution and infection mechanisms. We focused on wastewater samples, as potential sources of phages infecting various Bacteroides hosts. Sequencing, assembly, and characterization of isolated phages revealed 14 complete genomes belonging to three novel Crassvirales species infecting Bacteroides cellulosilyticus WH2. These species, Kehishuvirus sp. tikkala strain Bc01, Kolpuevirus sp. frurule strain Bc03, and Rudgehvirus jaberico strain Bc11, spanned two families, and three genera, displaying a broad range of virion productions. Upon testing all successfully cultured Crassvirales species and their respective bacterial hosts, we discovered that they do not exhibit co-evolutionary patterns with their bacterial hosts. Furthermore, we observed variations in gene similarity, with greater shared similarity observed within genera. However, despite belonging to different genera, the three novel species shared a unique structural gene that encodes the tail spike protein. When investigating the relationship between this gene and host interaction, we discovered evidence of purifying selection, indicating its functional importance. Moreover, our analysis demonstrated that this tail spike protein binds to the TonB-dependent receptors present on the bacterial host surface. Combining these observations, our findings provide insights into phage-host interactions and present three Crassvirales species as an ideal system for controlled infectivity experiments on one of the most dominant members of the human enteric virome. Impact statementBacteriophages play a crucial role in shaping microbial communities within the human gut. Among the most dominant bacteriophages in the human gut microbiome are Crassvirales phages, which infect Bacteroides. Despite being widely distributed, only a few Crassvirales genomes have been isolated, leading to a limited understanding of their biology, ecology, and evolution. This study isolated and characterized three novel Crassvirales genomes belonging to two different families, and three genera, but infecting one bacterial host, Bacteroides cellulosilyticus WH2. Notably, the observation confirmed the phages are not co-evolving with their bacterial hosts, rather have a shared ability to exploit similar features in their bacterial host. Additionally, the identification of a critical viral protein undergoing purifying selection and interacting with the bacterial receptors opens doors to targeted therapies against bacterial infections. Given Bacteroides role in polysaccharide degradation in the human gut, our findings advance our understanding of the phage-host interactions and could have important implications for the development of phage-based therapies. These discoveries may hold implications for improving gut health and metabolism to support overall well-being. Data summaryThe genomes used in this research are available on Sequence Read Archive (SRA) within the project, PRJNA737576. Bacteroides cellulosilyticus WH2, Kehishuvirus sp. tikkala strain Bc01, Kolpuevirus sp. frurule strain Bc03, and Rudgehvirus jaberico strain Bc11 are all available on GenBank with accessions NZ_CP072251.1 (B. cellulosilyticus WH2), QQ198717 (Bc01), QQ198718 (Bc03), and QQ198719 (Bc11), and we are working on making the strains available through ATCC. The 3D protein structures for the three Crassvirales genomes are available to download at doi.org/10.25451/flinders.21946034.

bioinformatics↗

bioRxiv2022

Hecatomb: An End-to-End Research Platform for Viral Metagenomics

BackgroundAnalysis of viral diversity using modern sequencing technologies offers extraordinary opportunities for discovery. However, these analyses present a number of bioinformatic challenges due to viral genetic diversity and virome complexity. Due to the lack of conserved marker sequences, metagenomic detection of viral sequences requires a non-targeted, random (shotgun) approach. Annotation and enumeration of viral sequences relies on rigorous quality control and effective search strategies against appropriate reference databases. Virome analysis also benefits from the analysis of both individual metagenomic sequences as well as assembled contigs. Combined, virome analysis results in large amounts of data requiring sophisticated visualization and statistical tools. ResultsHere we introduce Hecatomb, a bioinformatics platform enabling both read and contig based analysis. Hecatomb integrates query information from both amino acid and nucleotide reference sequence databases. Hecatomb integrates data collected throughout the workflow enabling analyst driven virome analysis and discovery. Hecatomb is available on GitHub at https://github.com/shandley/hecatomb. ConclusionsHecatomb provides a single, modular software solution to the complex tasks required of many virome analysis. We demonstrate the value of the approach by applying Hecatomb to both a host-associated (enteric) and an environmental (marine) virome data set. Hecatomb provided data to determine true- or false-positive viral sequences in both data sets and revealed complex virome structure at distinct marine reef sites.

bioinformatics↗

bioRxiv2019

Genomics to aid species delimitation and effective conservation of the Sharpnose Guitarfish (Glaucostegus granulatus)

The Sharpnose Guitarfish (Glaucostegus granulatus) is one of fifteen critically endangered Rhino Rays which has been exploited as incidental catch, leading to severe population depletions and localized disappearances. Like many chondrichthyan species, there are no species-specific time-series data available for the Sharpnose Guitarfish that can be used to calculate population reduction, partly due to a lack of species-specific reporting as well as limitations in accurate taxonomic identification. We here present the first complete mitochondrial genome and partial nuclear genome of the species and the first detail phylogenetic assessment of the species. We expect that data presented in the current manuscript will aid in accurate species-specific landing and population assessments of the species in the future and will enable conservation efforts to protect and recover remaining populations.

genomics↗