AMRFinderPlus and the Reference Gene Catalog facilitate examination of the genomic links among antimicrobial resistance, stress response, and virulence

Authors: FELDGARDEN, MICHAEL - National Institutes Of Health (NIH); BROVER, VYACHESLAV - National Institutes Of Health (NIH); GONZALEZ-ESCALONA, NARJOL - Us Food & Drug Administration (FDA); Frye, Jonathan; HAENDIGES, JULIE - Us Food & Drug Administration (FDA); HAFT, DANIEL - National Institutes Of Health (NIH); PETTENGILL, JAMES - Us Food & Drug Administration (FDA); PRASAD, ARJUN - National Institutes Of Health (NIH); TILLMAN, GLENN - Food Safety Inspection Service (FSIS); TYSON, GREGORY - Us Food & Drug Administration (FDA); KLIMKE, WILLIAM - National Institutes Of Health (NIH)

Submitted to: Nature Scientific Reports
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/19/2021
Publication Date: 6/19/2021
Citation: Feldgarden, M., Brover, V., Gonzalez-Escalona, N., Frye, J.G., Haendiges, J., Haft, D.H., Pettengill, J.B., Prasad, A.B., Tillman, G.E., Tyson, G.H., Klimke, W. 2021. AMRFinderPlus and the Reference Gene Catalog facilitate examination of the genomic links among antimicrobial resistance, stress response, and virulence. Nature Scientific Reports. 11:12728. https://doi.org/10.1038/s41598-021-91456-0.
DOI: https://doi.org/10.1038/s41598-021-91456-0

Interpretive Summary: Antimicrobial resistance (AMR) in pathogenic bacteria is a significant public health threat. With whole genome sequencing (WGS) becoming affordable, WGS data can be used to determine the AMR gene content of a bacterial isolate by searching the DNA sequence for the presence of known resistance genes in a database. As part of a multi-agency collaboration to maximize the accuracy of AMR gene detection, the National Center for Biotechnology Information (NCBI) developed the Bacterial Antimicrobial Resistance Reference Gene Database and the AMR gene detection tool AMRFinder. The database is now called the Reference Gene Catalog, and includes acid, biocide, metal, stress resistance, and virulence genes and also species-specific point mutations. Genes and point mutations are classified by broad and detailed functions. To capitalize on this expanded database of genes and their functions, NCBI released AMRFinderPlus. This new tool allows the users to use only the core set of AMR elements or include stress response and virulence genes too. AMRFinderPlus can detect acquired genes and point mutations in both protein and nucleotide sequence. The evidence used to identify the genes has been expanded to include whether nucleotide or protein sequence was used, the gene's location in the contig, and possession of an internal stop. These database improvements and functional expansions will enable increased precision in identifying AMR genes, linking AMR genotypes and phenotypes, and determining possible relationships between AMR, virulence, and stress response.

Technical Abstract: Antimicrobial resistance (AMR) is a significant public health threat. With the rise of affordable whole genome sequencing, in silico approaches to assessing AMR gene content can be used to assess the presence of existing resistance mechanisms and potentially identify novel mechanisms. To enable accurate assessment of AMR gene content, as part of a multi-agency collaboration, the National Center for Biotechnology Information (NCBI) developed a comprehensive AMR gene database, the Bacterial Antimicrobial Resistance Reference Gene Database and the AMR gene detection tool AMRFinder. Here, we describe the expansion of the Reference Gene Database, now called the Reference Gene Catalog, to include putative acid, biocide, metal, stress resistance genes, in addition to virulence genes and species-specific point mutations. Genes and point mutations are classified by broad function, as well as more detailed functions. As we have expanded both the functional repertoire of identified genes and functionality, NCBI released a new version of AMRFinder, known as AMRFinderPlus. This new tool allows the users the option to use only the core set of AMR elements, or include stress response and virulence genes too. AMRFinderPlus can detect acquired genes and point mutations in both protein and nucleotide sequence. In addition, the evidence used to identify the gene has been expanded to include whether nucleotide or protein sequence was used, its location in the contig, and possession of an internal stop. These database improvements and functional expansions will enable increased precision in identifying AMR genes, linking AMR genotypes and phenotypes, and determining possible relationships between AMR, virulence and stress response.