bioRxiv ScienceSearch

Biology subjects

Matthew B Sullivan

Publications and source records attributed to Matthew B Sullivan.

3 recordsLinked to original sources

Phages rarely encode antibiotic resistance genes: a cautionary tale for virome analysis

Antibiotic resistance genes (ARG) are pervasive in gut microbiota, but it remains unclear how often ARG are transferred, particularly to pathogens. Traditionally, ARG spread is attributed to horizontal transfer mediated either by DNA transformation, bacterial conjugation or generalized transduction. However, recent viral metagenome (virome) analyses suggest that ARG are frequently carried by phages, which is inconsistent with the traditional view that phage genomes rarely encode ARG. Here we used exploratory and conservative bioinformatic strategies found in the literature to detect ARG in phage genomes, and experimentally assessed a subset of ARG predicted using exploratory thresholds. ARG abundances in 1,181 phage genomes were vastly over-estimated using exploratory thresholds (421 predicted vs 2 known), due to low similarities and matches to protein unrelated to antibiotic resistance. Consistent with this, 4 ARG predicted using exploratory thresholds were experimentally evaluated and failed to confer antibiotic resistance in Escherichia coli. Re-analysis of available human-or mouse-associated viromes for ARG and their genomic context suggested that bona fide ARG attributed to phages in viromes were previously over-estimated. These findings provide guidance for documentation of ARG in viromes, and re-assert that ARG are rarely encoded in phages.

Ecology

Ecogenomics and biogeochemical impacts of uncultivated globally abundant ocean viruses

Ocean microbes drive global-scale biogeochemical cycling1, but do so under constraints imposed by viruses on host community composition, metabolism, and evolutionary trajectories2-5. Due to sampling and cultivation challenges, genome-level viral diversity remains poorly described and grossly understudied in nature such that <1% of observed surface ocean viruses, even those that are abundant and ubiquitous, are known5. Here we analyze a global map of abundant, double stranded DNA (dsDNA) viruses and viral-encoded auxiliary metabolic genes (AMGs) with genomic and ecological contexts through the Global Ocean Viromes (GOV) dataset, which includes complete genomes and large genomic fragments from both surface and deep ocean viruses sampled during the Tara Oceans and Malaspina research expeditions6,7. A total of 15,222 epi- and mesopelagic viral populations were identified that comprised 867 viral clusters (VCs, approximately genus-level groups8,9). This roughly triples known ocean viral populations10, doubles known candidate bacterial and archaeal virus genera9, and near-completely samples epipelagic communities at both the population and VC level. Thirty-eight of the 867 VCs were identified as the most impactful dsDNA viral groups in the oceans, as these were locally or globally abundant and accounted together for nearly half of the viral populations in any GOV sample. Most of these were predicted in silico to infect dominant, ecologically relevant microbes, while two thirds of them represent newly described viruses that lacked any cultivated representative. Beyond these taxon-specific ecological observations, we identified 243 viral-encoded AMGs in GOV, only 95 of which were known. Deeper analyses of 4 of these AMGs revealed that abundant viruses directly manipulate sulfur and nitrogen cycling, and do so throughout the epipelagic ocean. Together these data provide a critically-needed organismal catalog and functional context to begin meaningfully integrating viruses into ecosystem models as key players in nutrient cycling and trophic networks.

Ecology

iVirus: facilitating new insights in viral ecology with software and community datasets imbedded in a cyberinfrastructure

Microbes impact nutrient and energy transformations throughout the worlds ecosystems, yet they do so under viral constraints. In complex communities, viral metagenome (virome) sequencing is transforming our ability to quantify viral diversity and impacts. While some bottlenecks, e.g., few reference genomes and non-quantitative viromics, have been overcome, the void of centralized datasets and specialized tools now prevents viromics from being broadly applied to answer fundamental ecological questions. Here we present iVirus, a community resource that leverages the CyVerse cyberinfrastructure to provide access to viromic tools and datasets. The iVirus Data Commons contains both raw and processed data from 1866 samples and 73 projects derived from global ocean expeditions, as well as existing and legacy public repositories. Through the CyVerse Discovery Environment, users can interrogate these datasets using existing analytical tools (software applications known as \"Apps\") for assembly, ORF prediction, and annotation, as well as several new Apps specifically developed for analyzing viromes. Because Apps are web-based and powered by CyVerse super-computing resources, they enable scalable analyses for a broad user base. Finally, a use-case scenario documents how to apply these advances towards new data. This growing iVirus resource should help researchers utilize viromics as yet another tool to elucidate viral roles in nature.

Bioinformatics