Speicher, D.J., K. Luinstra, J. Maciejewski, K.K. Tsang, A.G. McArthur, & M. Smieja. 2019. Clostridioides difficile strain divergence over time. Oral presentation at the Association of Medical Microbiology and Infectious Disease Canada (AMMI Canada) & Canadian Association for Clinical Microbiology and Infectious Diseases (CACMID) Joint Annual Conference, Ottawa, Ontario.

Background: Clostridioides difficileinfection (CDI) is a serious hospital-associated infection with severe outbreaks caused by the hypervirulent NAP1/MLST-1 strain.  Whole genome sequencing has shown that most outbreak strains are clonal whereas non-outbreaks display a wide diversity of strains.  To examine strain diversity in clinical settings, a subset of C. difficileisolates from symptomatic CDI from an acute care hospital were compared to isolates from C. difficilecolonized (CDC) asymptomatic subjects from the same hospital.

Methods: A subset of PCR-positive stool samples from clinically confirmed CDI isolates from 2016 (13/110), 2017 (8/111), and 2018 (13/65), and CDC from 2017 (17/185) were cultured 3-times consecutively on CHROMagar™ C. difficile, sub-cultured on Columbia colistin-nalidixic acid (CNA) media, had DNA isolated, shotgun sequenced, and genome assembled for both MLST typing and genome-wide SNP phylogenetic analysis.

Results: Based on MLST profiles, the C. difficiletypes detected were diverse. Of the presumed binary toxin positive/NAP1 strains (i.e. PCR tcdA/tcdBpositive) 7/12 (58%) were NAP1/MLST-1 and 3/12 (25%) were NAP7/MLST-11.  NAP1/MLST-1 was not detected in any CDC isolate.  NAP4/MLST-2,14 were detected in 2016 (n=4), 2017 (n=2), 2018 (n=1), and in CDC isolates (n=3).  MLST-42 was dominant in CDC isolates (5/17; 29%) and decreased in prevalence in CDI isolates over time (2016=4; 2017=0; 2018=1).

Conclusion:  C. difficilestrains amongst both CDI and CDC individuals are highly divergent. Whilst molecular assays are misclassifying 25% of “NAP1” strains, both NAP1 and NAP7 are hypervirulent.  The number of MLST-42 CDC isolates is concerning as it has been reported to be the most common strain causing CDI among U.S. adults.  This highlights the need for continued genomic surveillance of both CDI and CDC individuals. Genome-wide SNP phylogenetic analysis is currently being performed.

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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.

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A week of lectures, demos, and training for the Comprehensive Antibiotic Resistance Database

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 card@mcmaster.ca

  


Workshop & Lecture material will be available herehttps://github.com/arpcard/state-of-the-card-2019


 

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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.

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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.

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4th year Bachelor of Health Sciences student Alexandra Florescu has joined us for her Biochem 3A03 (Biochemical Research Practice) course. Alexandra will be collaborating with colleagues in the Genomic Epidemiology Ontology Consortium (genepio.org) on developing ontological terminology for phenotypic tests of antimicrobial resistance and microbial virulence via our ongoing Genome Canada Bioinformatics & Computational Biology funding.

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Congratulations to this year’s crop of BiomedDC 4A15 thesis students for 8 month research projects well done! From left to right:

Suman Virdee – Developing a Galaxy based Pipeline for RNA-Seq Analysis in Stem Cell Biology

Kirill Pankov – The Cytochrome P450 (CYP) Superfamily in the Cnidarian Phylum

Jonsson Liu – Clinical virulence detection and Clostridium difficile clonality

Annie Cheng – Predicting Plasmid-Mediated Antimicrobial Resistance from Whole Genome Sequencing

Godwin Chan – Using the Galaxy Platform to Increase Accessibility for Structure Determination via Cryo-Electron Microscopy

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coverMcArthur AG & Tsang KK.

Ann N Y Acad Sci. 2017 Jan;1388(1):78-91.

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.

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I spent July travelling to two great meetings in the British Isles. First was the Galaxy Community Conference in Norwich, UK which provided a crash course on the Galaxy Platform for data analysis – data intensive biology for everyone! We will definitely be using Galaxy for projects in 2015-2016. Second was the 2015 Annual Conference on Intelligent Systems for Molecular Biology / European Conference on Computational Biology joint meeting in Dublin, Ireland. This meeting covers a very broad spectrum of computational biology and our work on the CARD was well received. I also got a change to attend the Bio-Ontologies SIG for the first time, which provided a lot of perspective for our ontology development efforts. And yes, I had a few pints with colleagues…

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  • McArthur, A.G. 2015. Flash Update – The Antibiotic Resistance Ontology. Presentation at Bio-Ontologies 2015, Dublin, Ireland.
  • McArthur, A.G., Waglechner, N., Nizam, F., Pereira, S.K., Jia, B., Sardar, D., Westman, E.L., Pawlowski, A.C., Johnson, T., Lo, R., Courtot, M., Brinkman, F.S., Williams, L.E., Frye, J.G., & Wright, G.D. 2015. The Comprehensive Antibiotic Resistance Database. Poster Presentation at the 23rd Annual International Conference on Intelligent Systems for Molecular Biology, Dublin, Ireland.
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