CARD 2020: antibiotic resistome surveillance with the comprehensive antibiotic resistance database
TL;DR: A new Resistomes & Variants module provides analysis and statistical summary of in silico predicted resistance variants from 82 pathogens and over 100 000 genomes, able to summarize predicted resistance using the information included in CARD, identify trends in AMR mobility and determine previously undescribed and novel resistance variants.
Abstract: The Comprehensive Antibiotic Resistance Database (CARD; https://card.mcmaster.ca) is a curated resource providing reference DNA and protein sequences, detection models and bioinformatics tools on the molecular basis of bacterial antimicrobial resistance (AMR). CARD focuses on providing high-quality reference data and molecular sequences within a controlled vocabulary, the Antibiotic Resistance Ontology (ARO), designed by the CARD biocuration team to integrate with software development efforts for resistome analysis and prediction, such as CARD's Resistance Gene Identifier (RGI) software. Since 2017, CARD has expanded through extensive curation of reference sequences, revision of the ontological structure, curation of over 500 new AMR detection models, development of a new classification paradigm and expansion of analytical tools. Most notably, a new Resistomes & Variants module provides analysis and statistical summary of in silico predicted resistance variants from 82 pathogens and over 100 000 genomes. By adding these resistance variants to CARD, we are able to summarize predicted resistance using the information included in CARD, identify trends in AMR mobility and determine previously undescribed and novel resistance variants. Here, we describe updates and recent expansions to CARD and its biocuration process, including new resources for community biocuration of AMR molecular reference data.
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TL;DR: In this article, the authors present the current understanding of the roles of the environment, including antibiotic pollution, in resistance evolution, in transmission and as a mere reflection of the regional antibiotic resistance situation in the clinic.
Abstract: Antibiotic resistance is a global health challenge, involving the transfer of bacteria and genes between humans, animals and the environment. Although multiple barriers restrict the flow of both bacteria and genes, pathogens recurrently acquire new resistance factors from other species, thereby reducing our ability to prevent and treat bacterial infections. Evolutionary events that lead to the emergence of new resistance factors in pathogens are rare and challenging to predict, but may be associated with vast ramifications. Transmission events of already widespread resistant strains are, on the other hand, common, quantifiable and more predictable, but the consequences of each event are limited. Quantifying the pathways and identifying the drivers of and bottlenecks for environmental evolution and transmission of antibiotic resistance are key components to understand and manage the resistance crisis as a whole. In this Review, we present our current understanding of the roles of the environment, including antibiotic pollution, in resistance evolution, in transmission and as a mere reflection of the regional antibiotic resistance situation in the clinic. We provide a perspective on current evidence, describe risk scenarios, discuss methods for surveillance and the assessment of potential drivers, and finally identify some actions to mitigate risks.
383 citations
TL;DR: The Metagenomic Gut Virus catalogue as discussed by the authors contains 189,680 genomes from 11,810 publicly available human stool metagenomes and identified 54,118 candidate viral species, 92% of which were not found in existing databases.
Abstract: Bacteriophages have important roles in the ecology of the human gut microbiome but are under-represented in reference databases. To address this problem, we assembled the Metagenomic Gut Virus catalogue that comprises 189,680 viral genomes from 11,810 publicly available human stool metagenomes. Over 75% of genomes represent double-stranded DNA phages that infect members of the Bacteroidia and Clostridia classes. Based on sequence clustering we identified 54,118 candidate viral species, 92% of which were not found in existing databases. The Metagenomic Gut Virus catalogue improves detection of viruses in stool metagenomes and accounts for nearly 40% of CRISPR spacers found in human gut Bacteria and Archaea. We also produced a catalogue of 459,375 viral protein clusters to explore the functional potential of the gut virome. This revealed tens of thousands of diversity-generating retroelements, which use error-prone reverse transcription to mutate target genes and may be involved in the molecular arms race between phages and their bacterial hosts.
159 citations
TL;DR: (meta)proteomics analysis of bacterial compartment of raw milk is applied to obtain a method that provides a measurement of circulating AMR involved proteins and gathers information about the whole bacterial composition.
Abstract: The environment, including animals and animal products, is colonized by bacterial species that are typical and specific of every different ecological niche. Natural and human-related ecological pressure promotes the selection and expression of genes related to antimicrobial resistance (AMR). These genes might be present in a bacterial consortium but might not necessarily be expressed. Their expression could be induced by the presence of antimicrobial compounds that could originate from a given ecological niche or from human activity. In this work, we applied (meta)proteomics analysis of bacterial compartment of raw milk in order to obtain a method that provides a measurement of circulating AMR involved proteins and gathers information about the whole bacterial composition. Results from milk analysis revealed the presence of 29 proteins/proteoforms linked to AMR. The detection of mainly β-lactamases suggests the possibility of using the milk microbiome as a bioindicator for the investigation of AMR. Moreover, it was possible to achieve a culture-free qualitative and functional analysis of raw milk bacterial consortia.
121 citations
Cites methods from "CARD 2020: antibiotic resistome sur..."
...Among other proteins with AMR potential identified using the CARD15 database there is an isoform of the Aminoglycoside N(6’)-acetyltransferase of Enterococcus hirae....
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...In order to identify the whole bacterial proteome, the obtained MS datasets were analyzed using different databases: UniProt KB/Swiss-Prot restricted to all reviewed Bacteria protein sequences (UniProt KB) and the Comprehensive Antibiotic Resistance Database (CARD) [14]....
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...Figure 3 shows the Venn diagram of the proteins identified in the two extractions using the CARD 15 database....
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...The same raw MS dataset was then searched against the CARD 15 database....
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...The qualitative identification of proteins was obtained by searching two different databases: (i) bacteria (UniProt KB/Swiss-Prot Protein Knowledgebase restricted to all Bacteria taxonomy) and (ii) The Comprehensive AMR Database (CARD, https://card.mcmaster.ca/) as FASTA files [13,14]....
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TL;DR: In this paper , the authors present a platform consisting of three modules, which are preconfigured bioinformatic pipelines, cloud toolsets, and online omics' courses, which combine analytic tools for metagenomics, genomes, transcriptome, proteomics and metabolomics.
Abstract: The platform consists of three modules, which are pre-configured bioinformatic pipelines, cloud toolsets, and online omics' courses. The pre-configured bioinformatic pipelines not only combine analytic tools for metagenomics, genomes, transcriptome, proteomics and metabolomics, but also provide users with powerful and convenient interactive analysis reports, which allow them to analyze and mine data independently. As a useful supplement to the bioinformatics pipelines, a wide range of cloud toolsets can further meet the needs of users for daily biological data processing, statistics, and visualization. The rich online courses of multi-omics also provide a state-of-art platform to researchers in interactive communication and knowledge sharing.
121 citations
University of Dhaka1, Loyola University Chicago2, BGC Trust University Bangladesh3, Indian Veterinary Research Institute4, Mawlana Bhashani Science and Technology University5, University of Szeged6, Sarhad University of Science & IT, Ring Road (Hayatabad Link) Peshawar7, State University of Bangladesh8, Kathmandu9
TL;DR: Antibiotics have been used to cure bacterial infections for more than 70 years, and these low-molecular-weight bioactive agents have also been used for a variety of other medicinal applications.
99 citations
References
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TL;DR: Effective treatment of resistant infections, antimicrobial stewardship, and new drug discovery increasingly rely upon genotype information, powered by decreasing costs of DNA sequencing, which requires advances in microbial informatics.
76 citations
"CARD 2020: antibiotic resistome sur..." refers methods in this paper
...With the increasing use of genome sequencing as a surveillance tool for AMR molecular epidemiology (10,11), as well as the targeting of specific AMR genes by novel adjuvants (12), databases and clear nomenclature for AMR gene families is critical....
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Critical Path Institute1, University of Valencia2, Simon Fraser University3, Centers for Disease Control and Prevention4, World Health Organization5, Stellenbosch University6, John Radcliffe Hospital7, Swiss Tropical and Public Health Institute8, Karolinska Institutet9, Spanish National Research Council10, Translational Genomics Research Institute11, Rutgers University12, Institute of Tropical Medicine Antwerp13, University of Cape Town14, Aga Khan University15, University of California, San Diego16
TL;DR: A unified analysis variant pipeline (UVP) was developed to identify variants and assign lineage from MTBC sequence data and has an above 94% accuracy of predicting drug based on the accompanying DST results in the ReSeqTB platform.
Abstract: Drug-resistant tuberculosis poses a persistent public health threat. The ReSeqTB platform is a collaborative, curated knowledgebase, designed to standardize and aggregate global Mycobacterium tuberculosis complex (MTBC) variant data from whole genome sequencing (WGS) with phenotypic drug susceptibility testing (DST) and clinical data. We developed a unified analysis variant pipeline (UVP) ( https://github.com/CPTR-ReSeqTB/UVP ) to identify variants and assign lineage from MTBC sequence data. Stringent thresholds and quality control measures were incorporated in this open source tool. The pipeline was validated using a well-characterized dataset of 90 diverse MTBC isolates with conventional DST and DNA Sanger sequencing data. The UVP exhibited 98.9% agreement with the variants identified using Sanger sequencing and was 100% concordant with conventional methods of assigning lineage. We analyzed 4636 publicly available MTBC isolates in the ReSeqTB platform representing all seven major MTBC lineages. The variants detected have an above 94% accuracy of predicting drug based on the accompanying DST results in the platform. The aggregation of variants over time in the platform will establish confidence-graded mutations statistically associated with phenotypic drug resistance. These tools serve as critical reference standards for future molecular diagnostic assay developers, researchers, public health agencies and clinicians working towards the control of drug-resistant tuberculosis.
74 citations
"CARD 2020: antibiotic resistome sur..." refers background in this paper
...tuberculosis AMR will be a major focus in 2020, including harmonization with ReSeqTB (33), as CARD currently has curation gaps for this pathogen....
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...Biocuration of M. tuberculosis AMR will be a major focus in 2020, including harmonization with ReSeqTB (33), as CARD currently has curation gaps for this pathogen....
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TL;DR: The creation of novel AMR bioinformatics tools and databases and their continued development will advance the understanding of the molecular mechanisms and threat severity of antibiotic resistance, while simultaneously improving the ability to accurately predict and screen for antibiotic resistance genes within environmental, agricultural, and clinical settings.
Abstract: The loss of effective antimicrobials is reducing our ability to protect the global population from infectious disease. However, the field of antibiotic drug discovery and the public health monitoring of antimicrobial resistance (AMR) is beginning to exploit the power of genome and metagenome sequencing. The creation of novel AMR bioinformatics tools and databases and their continued development will advance our understanding of the molecular mechanisms and threat severity of antibiotic resistance, while simultaneously improving our ability to accurately predict and screen for antibiotic resistance genes within environmental, agricultural, and clinical settings. To do so, efforts must be focused toward exploiting the advancements of genome sequencing and information technology. Currently, AMR bioinformatics software and databases reflect different scopes and functions, each with its own strengths and weaknesses. A review of the available tools reveals common approaches and reference data but also reveals gaps in our curated data, models, algorithms, and data-sharing tools that must be addressed to conquer the limitations and areas of unmet need within the AMR research field before DNA sequencing can be fully exploited for AMR surveillance and improved clinical outcomes.
70 citations
"CARD 2020: antibiotic resistome sur..." refers background or methods in this paper
...With the increasing use of genome sequencing as a surveillance tool for AMR molecular epidemiology (10,11), as well as the targeting of specific AMR genes by novel adjuvants (12), databases and clear nomenclature for AMR gene families is critical....
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...Given the severity of the AMR crisis and the next-generation sequencing revolution, it is no surprise that there is a large diversity of AMR databases and software tools available (10,13)....
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TL;DR: John Snow was one of the founders of epidemiology and his hypothesis that cholera was spread by contaminated water was tested by the 'Broad Street' epidemic of 1854, which showed that use of water from the Broad Street pump was strongly correlated with death from cholERA.
63 citations
TL;DR: A pipeline that contributes to the improved capacity for antimicrobial resistance detection afforded by next generation sequencing technologies, allowing for rapid detection of antimicrobial resistant genes directly from sequencing data is developed.
Abstract: Background
Antimicrobial resistance remains a growing and significant concern in human and veterinary medicine. Current laboratory methods for the detection and surveillance of antimicrobial resistant bacteria are limited in their effectiveness and scope. With the rapidly developing field of whole genome sequencing beginning to be utilised in clinical practice, the ability to interrogate sequencing data quickly and easily for the presence of antimicrobial resistance genes will become increasingly important and useful for informing clinical decisions. Additionally, use of such tools will provide insight into the dynamics of antimicrobial resistance genes in metagenomic samples such as those used in environmental monitoring.
61 citations
"CARD 2020: antibiotic resistome sur..." refers methods in this paper
...Others re-package the content of other AMR databases to provide an alternative database (17), tool (18) or statistical model (19)....
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