An omics-based framework for assessing the health risk of antimicrobial resistance genes

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Aug. 6, 2021

Abstract Antibiotic resistance genes (ARGs) are widespread among bacteria. However, not all ARGs pose serious threats to public health, highlighting the importance of identifying those that high-risk. Here, we developed an ‘omics-based’ framework evaluate ARG risk considering human-associated-enrichment, gene mobility, and host pathogenicity. Our classifies human-associated, mobile (3.6% ARGs) as highest risk, which further differentiate ‘current threats’ (Rank I; 3%) - already present pathogens ‘future II; 0.6%) novel emerging from non-pathogens. identified 73 threat’ families. Of these, 35 were 37 high-risk proposed by World Health Organization other literature; remaining 38 significantly enriched in hospital plasmids. By evaluating pathogen genomes released since construction, confirmed recently transferred into Rank II (‘future threats’). Lastly, applied gut microbiome fecal microbiota transplantation donors. We found although (73% genomes), only 8.9% contained ARGs. provides easy-to-implement approach identify current future antimicrobial threats, with potential clinical applications including reducing microbiome-based interventions.

Language: Английский

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AutoMLST: an automated web server for generating multi-locus species trees highlighting natural product potential

Nucleic Acids Research, Journal Year: 2019, Volume and Issue: 47(W1), P. W276 - W282

Published: April 11, 2019

Abstract Understanding the evolutionary background of a bacterial isolate has applications for wide range research. However generating an accurate species phylogeny remains challenging. Reliance on 16S rDNA identification currently popular. Unfortunately, this widespread method suffers from low resolution at level due to high sequence conservation. Currently, there is now wealth genomic data that can be used yield more designations via modern phylogenetic methods and multiple genetic loci. However, these often require extensive expertise time. The Automated Multi-Locus Species Tree (autoMLST) was thus developed provide rapid ‘one-click’ pipeline simplify workflow at: https://automlst.ziemertlab.com. This server utilizes Sequence Analysis (MLSA) produce high-resolution trees; does not preform multi-locus typing (MLST), related classification method. resulting tree also includes helpful annotations, such as clade secondary metabolite counts aid natural product prospecting. Distinct available web-interfaces, autoMLST automate selection reference genomes out-group organisms based one or query genomes. enables researchers perform rigorous analyses rapidly compared manual MLSA workflows.

Language: Английский

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Conjugative plasmids interact with insertion sequences to shape the horizontal transfer of antimicrobial resistance genes

Proceedings of the National Academy of Sciences, Journal Year: 2021, Volume and Issue: 118(6)

Published: Feb. 1, 2021

Significance There is great interest in understanding how antibiotic resistance disseminated by MGEs (i.e., plasmids, insertion sequences, and integrons). We have systematically investigated their interactions mediating the horizontal transfer of combining silico genomic analysis a large collection complete bacterial plasmids (14,029) genomes (12,059), then confirmed we observe nature using direct experimental approaches. showed whole picture all IS-associated patterns AMR genes across different genetic backgrounds our results highlight significant relationships between conjugative ISs shaping dissemination genes.

Language: Английский

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Metagenomic and metatranscriptomic analyses reveal activity and hosts of antibiotic resistance genes in activated sludge

Environment International, Journal Year: 2019, Volume and Issue: 129, P. 208 - 220

Published: May 23, 2019

Wastewater treatment plants (WWTPs) are a source and reservoir for subsequent spread of various antibiotic resistance genes (ARGs). However, little is known about the activity hosts ARGs in WWTPs. Here, we utilized both metagenomic metatranscriptomic approaches to comprehensively reveal diversity, abundance, expression activated sludge (AS) from three conventional WWTPs Taiwan. Based on deep sequencing data custom-made ARG database, total 360 associated with 24 classes antibiotics were identified AS metagenomes, an abundance range 7.06 × 10−1–1.20 10−4 copies ARG/copy 16S rRNA gene. Differential coverage binning analysis revealed that >22 bacterial phyla putative ARGs. Surprisingly, genus Mycobacterium family Burkholderiaceae observed as multi-drug resistant harboring 14 50 Metatranscriptome showed 65.8% being expressed, highlighting not only present, but also transcriptionally active AS. Remarkably, 110 annotated plasmid-associated displayed close two-fold increased likelihood expressed compared those found exclusively within chromosomes. Further transcript aminoglycoside, sulfonamide, tetracycline was mainly contributed by plasmid-borne Our approach allowed us specifically link their transcripts genetic context, providing comprehensive insight into prevalence, Overall, results this study enhance our understanding distribution dissemination WWTPs, which benefits environmental risk assessment management ARB

Language: Английский

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IntegronFinder 2.0: Identification and Analysis of Integrons across Bacteria, with a Focus on Antibiotic Resistance in Klebsiella

Microorganisms, Journal Year: 2022, Volume and Issue: 10(4), P. 700 - 700

Published: March 24, 2022

Integrons are flexible gene-exchanging platforms that contain multiple cassettes encoding accessory genes whose order is shuffled by a specific integrase. embedded within mobile genetic elements often antibiotic resistance they spread among nosocomial pathogens and contribute to the current crisis. However, most integrons presumably sedentary encode much broader diversity of functions. IntegronFinder widely used software identify novel in bacterial genomes, but has aged lacks some useful functionalities handle very large datasets draft genomes or metagenomes. Here, we present version 2. We have updated code, improved its efficiency usability, adapted output incomplete genome data, added few describe these changes illustrate relevance program analyzing distribution across more than 20,000 fully sequenced genomes. also take full advantage capabilities analyze close 4000 Klebsiella pneumoniae for presence them. Our data show K. largest integron our database plasmids. The pangenome contains total 165 different gene families with being related numerous types antibiotics. free open-source available on public platforms.

Language: Английский

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PCycDB: a comprehensive and accurate database for fast analysis of phosphorus cycling genes

Microbiome, Journal Year: 2022, Volume and Issue: 10(1)

Published: July 4, 2022

Abstract Background Phosphorus (P) is one of the most essential macronutrients on planet, and microorganisms (including bacteria archaea) play a key role in P cycling all living things ecosystems. However, our comprehensive understanding genes (PCGs) (PCMs) as well their ecological functions remains elusive even with rapid advancement metagenome sequencing technologies. One major challenges lack accurately annotated functional gene database. Results In this study, we constructed well-curated database (PCycDB) covering 139 families 10 metabolic processes, including several previously ignored PCGs such pafA encoding phosphate-insensitive phosphatase, ptxABCD (phosphite-related genes), novel aepXVWPS for 2-aminoethylphosphonate transporters. We achieved an annotation accuracy, positive predictive value (PPV), sensitivity, specificity, negative (NPV) 99.8%, 96.1%, 99.9%, respectively, simulated datasets. Compared to other orthology databases, PCycDB more accurate, comprehensive, faster profile PCGs. used analyze microbial communities from representative natural engineered environments showed that could apply different environments. Conclusions demonstrate powerful tool advancing microbially driven environment high coverage, analysis data. The available at https://github.com/ZengJiaxiong/Phosphorus-cycling-database .

Language: Английский

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ARGs-OAP v3.0: Antibiotic-Resistance Gene Database Curation and Analysis Pipeline Optimization

Engineering, Journal Year: 2022, Volume and Issue: 27, P. 234 - 241

Published: Dec. 27, 2022

Antibiotic resistance, which is encoded by antibiotic-resistance genes (ARGs), has proliferated to become a growing threat public health around the world. With technical advances, especially in popularization of metagenomic sequencing, scientists have gained ability decipher profiles ARGs diverse samples with high accuracy at an accelerated speed. To analyze thousands high-throughput way, standardized and integrated pipelines are needed. The new version (v3.0) widely used online analysis pipeline (ARGs-OAP) made significant improvements both reference database—the structured (SARG) database—and pipeline. SARG been enhanced sequence curation improve annotation reliability, incorporate emerging resistance genotypes, determine rigorous mechanism classification. database further organized visualized format tree-like structure dictionary. It also divided into sub-databases for different application scenarios. In addition, ARGs-OAP improved adjusted quantification methods, simplified tool implementation, multiple functions user-defined databases. Moreover, platform now provides biostatistical workflow visualization packages efficient interpretation ARG profiles. v3.0 will benefit academia, governmental management, consultation regarding risk assessment environmental prevalence ARGs.

Language: Английский

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Population-level impacts of antibiotic usage on the human gut microbiome

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: March 2, 2023

Abstract The widespread usage of antimicrobials has driven the evolution resistance in pathogenic microbes, both increased prevalence antimicrobial genes (ARGs) and their spread across species by horizontal gene transfer (HGT). However, impact on wider community commensal microbes associated with human body, microbiome, is less well understood. Small-scale studies have determined transient impacts antibiotic consumption but we conduct an extensive survey ARGs 8972 metagenomes to determine population-level impacts. Focusing 3096 gut microbiomes from healthy individuals not taking antibiotics demonstrate highly significant correlations between total ARG abundance diversity per capita rates ten countries spanning three continents. Samples China were notable outliers. We use a collection 154,723 human-associated metagenome assembled genomes (MAGs) link these taxa detect HGT. This reveals that are multi-species mobile shared pathogens commensals, within connected central component network MAGs ARGs. also observe individual profiles cluster into two types or resistotypes. frequent resistotype higher overall abundance, certain classes resistance, linked species-specific Proteobacteria periphery network.

Language: Английский

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Inter-plasmid transfer of antibiotic resistance genes accelerates antibiotic resistance in bacterial pathogens

The ISME Journal, Journal Year: 2024, Volume and Issue: 18(1)

Published: Jan. 1, 2024

Abstract Antimicrobial resistance is a major threat for public health. Plasmids play critical role in the spread of antimicrobial via horizontal gene transfer between bacterial species. However, it remains unclear how plasmids originally recruit and assemble various antibiotic genes (ARGs). Here, we track ARG recruitment assembly clinically relevant by combining systematic analysis 2420 complete plasmid genomes experimental validation. Results showed that across prevalent, 87% ARGs were observed to potentially among 8229 plasmid-borne ARGs. Interestingly, occur mostly compatible within same cell, with over 88% transfers occurring plasmids. Integron insertion sequences drive ongoing acquisition plasmids, especially which IS26 facilitates 63.1% events In vitro experiment validated important involved transferring gentamicin aacC1 Network four beta-lactam (blaTEM-1, blaNDM-4, blaKPC-2, blaSHV-1) shuffling 1029 45 clinical pathogens, suggesting alarming transferred accelerate propagation pathogens. are also able transmit environmental boundaries, terms high-sequence similarities This study demonstrated inter-plasmid universal mechanism ARGs, thus advancing our understanding emergence multidrug-resistant

Language: Английский

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Bacteria and Antibiotic Resistance Genes (ARGs) in PM_2.5 from China: Implications for Human Exposure

Environmental Science & Technology, Journal Year: 2018, Volume and Issue: 53(2), P. 963 - 972

Published: Dec. 10, 2018

Airborne transmission is one of the environmental dissemination pathways antibiotic resistance genes (ARGs), and has critical implications for human exposure through inhalation. In this study, we focused on three regions China to reveal some unique spatiotemporal features airborne bacteria ARGs in fine aerosols (PM2.5): (1) greater seasonal variations abundance temperate urban Beijing than subtropical areas Yangtze River Delta (YRD) Pearl (PRD) regions, with regional disparities bacterial communities; (2) geographical fingerprints ARG profiles independent cycles land-use gradients within each region; (3) region-independent associations between targeted limited genera; (4) common correlations mobile genetic elements (MGEs) across regions; (5) PM2.5 at higher end enrichment various media. The spatiotemporally differentiated communities abundances, compositions, mobility, potential hosts atmosphere have strong inhalational over scales. By comparing other contributing intake (e.g., drinking water food ingestion) U.S.A., identified region-specific importance inhalation as well country-specific scenarios. Our study thus highlights significance an integral part aggregate environmentally disseminated ARGs, which, turn, may help formulation adaptive strategies mitigate risks beyond.

Language: Английский

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