What is CARD?

The Comprehensive Antibiotic Resistance Database (CARD, Alcock et al., 2023) is a bioinformatics resource with information about antibiotic resistance genes, their products, and mechanisms of antibiotic resistance. This resource uses sequence analysis tools and rigorous literature based curation to classify the antibiotic resistance genes and variants that render antibiotic resistance. In addition, associated antibiotics, and their mechanisms of conferring resistance are also presented in the resource using the Antibiotic Resistance Ontology (ARO, McArthur et al., 2013).
The CARD browser available at RCSB.org presents protein sequences of PDB structures matched against Protein Homolog Models (curated reference sequences) from CARD. Exact matches in sequence represent instances of AMR genes that confer resistance through their presence in an organism - for example, the presence of a beta-lactamase gene on a plasmid. PDB sequences where 80% of the sequence (coverage) is at least 95% identical (sequence identity) to a CARD reference sequence, are annotated with the Antibiotic Resistance Ontology (ARO) terms for the gene family.

Why use the CARD Browser?

The CARD browser can help identify various antibiotic resistance genes (and proteins), gene families, organisms that commonly have the gene, and explore the mechanisms of action of the gene product. Thus CARD annotations can not only help with identifying Antibiotic Resistance Determinants, they provide additional information about organisms where this gene may be found, classes of drugs impacted and novel perspectives about its function.

How to use the CARD Browser?

There are three ways to identify an entry with CARD annotation:

• By browsing through the ARO classifications for determinants of antibiotics resistance, gene family, and gene etc.
• By typing and ARO identifier e.g., ARO:3000020
• By typing in the name of the protein(s) involved in Antibiotic resistance. e.g., beta-lactamase

After locating the individual or gene family of interest in the browser, users can view the number of PDB structures in this group. Clicking on the numbers listed next to the process name will launch a search for the PDB structures that have the CARD ARO domain of interest.

Note: Actual antibiotics (small molecules, peptides, and BIRD molecules) and Computed Structure Models are not assigned CARD annotations. Also proteins that confer antibiotic resistance but do not have a sufficient degree of sequence similarity with a CARD reference sequence for automatic detection (for example, 2X71 beta-lactamase structure doesn’t have CARD annotations because the sequence has only a 72% identity match with an ARO term (BcIII), and only 84% coverage).

Examples

Browse the PDB for structures of IMP-1 as follows:

• Navigate through the two trees (browsing entry points) and its branches for “Antibiotic inactivating enzyme” >> “Class B (Metallo)-beta lactamase” >> “subclass B1 (metallo-) beta-lactamase “ >> “IMP beta-lactamase” and "IMP-1" OR
• Type "IMP-1" in the search box on the top of the page and select from the options "IMP-1: 3002192", OR
• Type the ARO ID (3002192) in the search box on the top of the page

References:

• Alcock BP, Huynh W, Chalil R, Smith KW, Raphenya AR, Wlodarski MA, Edalatmand A, Petkau A, Syed SA, Tsang KK, Baker SJC, Dave M, McCarthy MC, Mukiri KM, Nasir JA, Golbon B, Imtiaz H, Jiang X, Kaur K, Kwong M, Liang ZC, Niu KC, Shan P, Yang JYJ, Gray KL, Hoad GR, Jia B, Bhando T, Carfrae LA, Farha MA, French S, Gordzevich R, Rachwalski K, Tu MM, Bordeleau E, Dooley D, Griffiths E, Zubyk HL, Brown ED, Maguire F, Beiko RG, Hsiao WWL, Brinkman FSL, Van Domselaar G, McArthur AG. CARD 2023: expanded curation, support for machine learning, and resistome prediction at the Comprehensive Antibiotic Resistance Database. Nucleic Acids Res. 2023 Jan 6;51(D1):D690-D699. https://doi.org/10.1093/nar/gkac920
• McArthur AG, Waglechner N, Nizam F, Yan A, Azad MA, Baylay AJ, Bhullar K, Canova MJ, De Pascale G, Ejim L, Kalan L, King AM, Koteva K, Morar M, Mulvey MR, O'Brien JS, Pawlowski AC, Piddock LJ, Spanogiannopoulos P, Sutherland AD, Tang I, Taylor PL, Thaker M, Wang W, Yan M, Yu T, Wright GD. The comprehensive antibiotic resistance database. Antimicrob Agents Chemother. 2013 Jul;57(7):3348-57. https://doi.org/10.1128%2FAAC.00419-13