CARD 2020: antibiotic resistome surveillance with the comprehensive antibiotic resistance database

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.

Figure 1.

Overview of CARD’s Resistance Gene Identifier software and its role in generating the CARD Resistomes & Variants data. (A). CARD AMR detection models include a reference sequence, a curated BLAST(P/N) bit score cut-off, and, if applicable, mutations known to predict AMR. This example shows the model parameters curated for the metallo-ß-lactamase NDM-1 (NCBI GenBank accession CAZ39946.1, from Klebsiella pneumoniae plasmid pKpANDM-1 accession FN396876.1). (B). User-submitted queries are analyzed by RGI using detection models which generate an annotation organized by the Perfect, Strict and Loose (if selected) paradigm. Here, we show the predicted resistome and CARD generated visualizations identified from NCBI GenBank accession JN420336.1 (Klebsiella pneumoniae plasmid pNDM-MAR). (C). When performed across thousands of complete genome sequences, complete plasmid sequences and WGS assemblies for 82 pathogens, the resulting data is extracted and calculated to populate the CARD Resistomes & Variants module. (D). Illustration of ARO classification tagging for JN420336.1, allowing organization of RGI results by AMR Gene Family, Drug Class and Resistance Mechanism.