Proksee: in-depth characterization and visualization of bacterial genomes

Nucleic Acids Research, Год журнала: 2023, Номер 51(W1), С. W484 - W492

Опубликована: Май 4, 2023

Abstract Proksee (https://proksee.ca) provides users with a powerful, easy-to-use, and feature-rich system for assembling, annotating, analysing, visualizing bacterial genomes. accepts Illumina sequence reads as compressed FASTQ files or pre-assembled contigs in raw, FASTA, GenBank format. Alternatively, can supply accession previously generated map JSON then performs assembly (for raw data), generates graphical map, an interface customizing the launching further analysis jobs. Notable features of include unique informative metrics provided via custom reference database assemblies; deeply integrated high-performance genome browser viewing comparing results at individual base resolution (developed specifically Proksee); ever-growing list embedded tools whose be seamlessly added to searched explored other formats; option export maps, results, log data sharing research reproducibility. All these are carefully designed multi-server cloud-based that easily scale meet user demand ensures web server is robust responsive.

Язык: Английский

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Personalized bacteriophage therapy outcomes for 100 consecutive cases: a multicentre, multinational, retrospective observational study

Nature Microbiology, Год журнала: 2024, Номер 9(6), С. 1434 - 1453

Опубликована: Июнь 4, 2024

Abstract In contrast to the many reports of successful real-world cases personalized bacteriophage therapy (BT), randomized controlled trials non-personalized products have not produced expected results. Here we present outcomes a retrospective observational analysis first 100 consecutive BT difficult-to-treat infections facilitated by Belgian consortium in 35 hospitals, 29 cities and 12 countries during period from 1 January 2008 30 April 2022. We assessed how often positive clinical outcome (general efficacy) performed regression identify functional relationships. The most common indications were lower respiratory tract, skin soft tissue, bone infections, involved combinations 26 bacteriophages 6 defined cocktails, individually selected sometimes pre-adapted target causative bacterial pathogens. Clinical improvement eradication targeted bacteria reported for 77.2% 61.3% respectively. our dataset cases, was 70% less probable when no concomitant antibiotics used (odds ratio = 0.3; 95% confidence interval 0.127–0.749). vivo selection resistance vitro bacteriophage–antibiotic synergy documented 43.8% (7/16 patients) 90% (9/10) evaluated patients, observed combination antibiotic re-sensitization reduced virulence bacteriophage-resistant isolates that emerged BT. Bacteriophage immune neutralization 38.5% (5/13) screened patients. Fifteen adverse events reported, including seven non-serious drug reactions suspected be linked While is limited uncontrolled nature these data, it indicates can effective with inform design future trials. BT100 study, ClinicalTrials.gov registration: NCT05498363 .

Язык: Английский

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Long-read metagenomic sequencing reveals shifts in associations of antibiotic resistance genes with mobile genetic elements from sewage to activated sludge

Microbiome, Год журнала: 2022, Номер 10(1)

Опубликована: Янв. 29, 2022

There is concern that the microbially rich activated sludge environment of wastewater treatment plants (WWTPs) may contribute to dissemination antibiotic resistance genes (ARGs). We applied long-read (nanopore) sequencing profile ARGs and their neighboring illuminate fate in by comparing abundance, genetic locations, mobility potential, bacterial hosts within relative those influent sewage across five WWTPs from three continents.The abundances (gene copies per Gb reads, aka gc/Gb) all carried putative pathogens decreased 75-90% (192-605 (31-62 at WWTPs. Long reads enabled quantification percent abundance with potential (i.e., located on plasmids or co-located other mobile elements (MGEs)). The plasmid-associated four (from 40-73 31-68%), transposable, integrative, conjugative element hallmark showed similar trends. Most ARG-associated 0.35-13.52% while integrative transposable displayed slight increases two (1.4-2.4%). While resistome taxonomic compositions both shifted significantly, host phyla for chromosomal ARG classes remained relatively consistent, indicating vertical gene transfer via active biomass growth as key pathway dissemination.Overall, our results suggest process acted a barrier against proliferation most ARGs, persisted increased warrant further attention. Video abstract.

Язык: Английский

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Duplicated antibiotic resistance genes reveal ongoing selection and horizontal gene transfer in bacteria

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Фев. 16, 2024

Abstract Horizontal gene transfer (HGT) and duplication are often considered as separate mechanisms driving the evolution of new functions. However, mobile genetic elements (MGEs) implicated in HGT can copy themselves, so positive selection on MGEs could drive duplications. Here, we use a combination modeling experimental to examine this hypothesis long-read genome sequences tens thousands bacterial isolates its generality nature. Modeling experiments show that antibiotic duplicated resistance genes (ARGs) through MGE transposition. A key implication is ARGs should be enriched environments associated with use. To test this, examined distribution 18,938 complete genomes ecological metadata. Duplicated highly bacteria isolated from humans livestock. further an independent set 321 antibiotic-resistant clinical isolates. Our findings indicate encode functions undergoing horizontal microbial communities.

Язык: Английский

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Microplastic diversity increases the abundance of antibiotic resistance genes in soil

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Ноя. 12, 2024

The impact of microplastics on antibiotic resistance has attracted widespread attention. However, previous studies primarily focused the effects individual microplastics. In reality, diverse microplastic types accumulate in soil, and it remains less well studied whether diversity (i.e., variations color, shape or polymer type) can be an important driver increased gene (ARG) abundance. Here, we employed microcosm to investigate soil ARG dynamics through metagenomic analysis. Additionally, evaluated associated potential health risks by profiling virulence factor genes (VFGs) mobile genetic elements (MGEs). Our findings reveal that as increases, there is a corresponding rise abundance ARGs, VFGs MGEs. We further identified microbial adaptive strategies involving (changed diversity), community (increased specific microbes), functions (enriched metabolic pathways) correlate with may thus contribute dissemination. Additional global change factors, including fungicide application plant reduction, also contributed elevated suggest that, addition considering contamination levels, crucial monitor ecosystems due their role driving dissemination multiple pathways.

Язык: Английский

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Selection and horizontal gene transfer underlie microdiversity-level heterogeneity in resistance gene fate during wastewater treatment

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Июнь 26, 2024

Abstract Activated sludge is the centerpiece of biological wastewater treatment, as it facilitates removal sewage-associated pollutants, fecal bacteria, and pathogens from through semi-controlled microbial ecology. It has been hypothesized that horizontal gene transfer spread antibiotic resistance genes within treatment plant, in part because presence residual antibiotics sewage. However, there surprisingly little evidence to suggest select for at plants via or otherwise. We addressed role promoting using lab-scale sequencing batch reactors fed field-collected wastewater, metagenomic sequencing, our recently developed bioinformatic tool Kairos. Here, we found confirmatory fluctuating levels sewage are associated with genes, ecology, microdiversity-level differences fate activated sludge.

Язык: Английский

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EasyMetagenome: A user‐friendly and flexible pipeline for shotgun metagenomic analysis in microbiome research

iMeta, Год журнала: 2025, Номер unknown

Опубликована: Фев. 14, 2025

Abstract Shotgun metagenomics has become a pivotal technology in microbiome research, enabling in‐depth analysis of microbial communities at both the high‐resolution taxonomic and functional levels. This approach provides valuable insights diversity, interactions, their roles health disease. However, complexity data processing need for reproducibility pose significant challenges to researchers. To address these challenges, we developed EasyMetagenome, user‐friendly pipeline that supports multiple methods, including quality control host removal, read‐based, assembly‐based, binning, along with advanced genome analysis. The also features customizable settings, comprehensive visualizations, detailed parameter explanations, ensuring its adaptability across wide range scenarios. Looking forward, aim refine by addressing contamination issues, optimizing workflows third‐generation sequencing data, integrating emerging technologies like deep learning network analysis, further enhance accuracy. EasyMetageonome is freely available https://github.com/YongxinLiu/EasyMetagenome .

Язык: Английский

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Core defense hotspots within Pseudomonas aeruginosa are a consistent and rich source of anti-phage defense systems

Nucleic Acids Research, Год журнала: 2023, Номер 51(10), С. 4995 - 5005

Опубликована: Май 4, 2023

Bacteria use a diverse arsenal of anti-phage immune systems, including CRISPR-Cas and restriction enzymes. Recent advances in system discovery annotation tools have unearthed many unique often encoded horizontally transferred defense islands, which can be transferred. Here, we developed Hidden Markov Models (HMMs) for systems queried microbial genomes on the NCBI database. Out 30 species with >200 completely sequenced genomes, our analysis found Pseudomonas aeruginosa exhibits greatest diversity as measured by Shannon entropy. Using network to identify common neighbors identified two core hotspot loci (cDHS1 cDHS2). cDHS1 is up 224 kb (median: 26 kb) varied arrangements more than distinct across isolates, while cDHS2 has 24 6 kb). Both cDHS regions are occupied majority P. isolates. Most genes unknown function potentially representing new validated identifying novel (Shango) commonly cDHS1. Identifying flanking islands could simplify may represent popular landing spots MGEs carrying systems.

Язык: Английский

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Metagenomic surveillance of antibiotic resistome in influent and effluent of wastewater treatment plants located on the Qinghai-Tibetan Plateau

The Science of The Total Environment, Год журнала: 2023, Номер 870, С. 162031 - 162031

Опубликована: Фев. 4, 2023

Язык: Английский

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Retrospective, observational analysis of the first one hundred consecutive cases of personalized bacteriophage therapy of difficult-to-treat infections facilitated by a Belgian consortium

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Авг. 28, 2023

In contrast to the many reports of successful cases personalized bacteriophage therapy, randomized controlled trials non-personalized products did not bring expected results. Here, we present outcomes a retrospective, observational analysis first 100 consecutive therapy difficult-to-treat infections facilitated by Belgian consortium. The most common indications were lower respiratory tract, skin & soft tissue, and bone infections, involved combinations 26 bacteriophages, individually selected sometimes pre-adapted target causative bacterial pathogens. Clinical improvement eradication targeted bacteria reported for 77.2% 61.3% respectively. Eradication was 70% less probable when no concomitant antibiotics used (odds-ratio = 0.3; 95% confidence interval 0.127–0.749). vivo selection resistance in vitro bacteriophage-antibiotic synergy documented 43.8% (7/16 patients) 90% (9/10) evaluated patients, Bacteriophage immune neutralization observed 38.5% (5/13) screened patients. (BT100 study, ClinicalTrials.gov registration: NCT05498363 .)

Язык: Английский

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