PURPOSE: Antimicrobial resistance (AMR), especially multidrug resistance, is one of the most serious global threats facing public health. We performed a proof of concept study assessing the suitability of shotgun proteomics as a complementary approach to whole-genome sequencing (WGS) for detecting AMR determinants.
EXPERIMENTAL DESIGN: We used previously published shotgun proteomics and WGS data on four isolates of Campylobacter jejuni to perform AMR detection by searching the Comprehensive Antibiotic Resistance Database, and we assessed their detection ability relative to genomics screening and traditional phenotypic testing measured by minimum inhibitory concentration.
RESULTS: Both genomic and proteomic approaches identified the wild type and variant molecular determinants responsible for resistance to tetracycline and ciprofloxacin, in agreement with phenotypic testing. In contrast, the genomic method identified the presence of the β-lactamase gene, blaOXA-61 , in three isolates. However, its corresponding protein product was detected in only a single isolate, consistent with results obtained from phenotypic testing.
Alcock BP, Raphenya AR, Lau TTY, Tsang KK, Bouchard M, Edalatmand A, Huynh W, Nguyen A-LV, Cheng AA, Liu S, Min SY, Miroshnichenko A, Tran H-K, Werfalli RE, Nasir JA, Oloni M, Speicher DJ, Florescu A, Singh B, Faltyn M, Hernandez-Koutoucheva A, Sharma AN, Bordeleau E, Pawlowski AC, Zubyk HL, Dooley D, Griffiths E, Maguire F, Winsor GL, Beiko RG, Brinkman FSL, Hsiao WWL, Van Domselaar G, McArthur AG.
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.
Dr. McArthur and PhD student Kara Tsang taught together at the 2019 MacData Institute Summer School, with Dr. McArthur reviewing biocuration and bioinformatics for genomic surviellence of antimicrobial resistance and Kara following up with a lecture on machine learning techniques to predict clinical antimicrobial resistance from raw genomic sequence.
Also congratulations to Kara for being awarded a 2019 Faculty of Health Sciences Graduate Programs Excellence Award!
Updated August 6, 2019: Congratulations to Kara for also winning an Ontario Graduate Scholarship!
The Comprehensive Antibiotic Resistance Database has been updated, http://card.mcmaster.ca
CARD Curation: Expanded MCR, OXA & IMP beta-lactamase, and macrolide phosphotransferase (MPH) sequence curation. Updated nomenclature for MPHs and drug resistant dihydrofolate reductases (dfr). Updated classification of ADC beta-lactamases.
Ontologies: Addition of 518 draft virulence ontology (VIRO) terms.
Prevalence, Resistomes, & Variants: Expansion to 82 pathogens (more Brucella species), 81,000+ resistomes, and 173,000+ AMR allele sequences based on sequence data acquired from NCBI on 28-Feb-2019, analyzed using RGI 4.2.2 (DIAMOND homolog detection) and CARD 3.0.1.
During McMaster Spring Mid-Term Recess (February 18-24), the McArthur lab is pleased to present a series of lectures, demonstrations, and training sessions for the Comprehensive Antibiotic Resistance Database (card.mcmaster.ca) and its associated Resistance Gene Identifier (RGI) software, sponsored by the Michael G. DeGroote Institute for Infectious Disease Research (IIDR).
Questions? Email firstname.lastname@example.org
Workshop & Lecture material will be available here: https://github.com/arpcard/state-of-the-card-2019
Antimicrobial Resistance: Emergence, Transmission, and Ecology (ARETE). R. Beiko (PI; Dalhousie University), F. Brinkman (co-PI, Simon Fraser University), A.G. McArthur (co-Applicant) + 4 additional co-Applicants. Genome Canada Bioinformatics and Computational Biology Competition.
Bioinformatics Tools to Improve Data Sharing and Re-use in Public Health – applications in antimicrobial resistance profiling and source tracking. W. Hsiao (PI; University of British Columbia), A.G. McArthur (co-Applicant) + 8 additional co-Applicants. CIHR Project Grant.
Congratulations to #TeamVirulence for winning the 2018 McMaster Innovation Showcase People’s Choice Poster Award for their poster entitled, “Examining the relationship between virulence and antimicrobial resistance via expansion of the Comprehensive Antibiotic Resistance Database (CARD)”! Left to right: Anatoly MiroshnichenkoHiu-Ki Rachel Tran, Sally Yue Min, and Rafik El Werfalli.
#TeamVirulence also presented their work at the 2018 Michael G. DeGroote Institute for Infectious Disease Research (IIDR) Trainee Day!
Some invitations are more special than others. Dr. Peixoto da Cruz and I went to graduate school together in British Columbia (a long time ago!) and while we have since lived in different hemispheres, the bond remains strong. It was great to visit PUG Goiás and learn about Peixoto’s impressive training program in genetic screening and counselling, plus talk about our AMR surveillance efforts.
Bioinformatics of antimicrobial resistance in the age of molecular epidemiology. Invited Keynote presentation by A.G. McArthur at Reunião de Citogenética do Brasil Central & XII Workshop de Genética da PUC Goiás, Goiânia, Brazil, October 2018.
Welcome #TeamVirulence, left to right: Rachel Tran (Biochem 3R06), Sally Min (BiomedDC 4A15), Anatoly Miroshnichencko (BiomedDC 4A15), and Rafik El Werfalli (BiomedDC 4A15), who are collectively working on development of CARD:Virulence, a new branch of the Comprehensive Antibiotic Resistance Database dedicated to the molecular surveillance of bacterial virulence factors.