briony lagoThis month we say farewell to Briony Lago as she returns to her undergraduate studies in Chemical Biology at McMaster. Briony joined us as part of her Chemical Biology Co-Op program and worked on both human muscle atrophy and zebrafish toxicology transcriptome studies, as well a curation of the Comprehensive Antibiotic Resistance Database. Her publications are below, with more on the way. Briony was also awarded a 2016 IIDR Summer Student Fellowship for her work. Good luck Briony!

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header-aa7f836a57fbef4ef15c560ab4ce386fPawlowski AC, Wang W, Koteva K, Barton HA, McArthur AG, & Wright GD.

Nat Commun. 2016 Dec 8;7:13803.

Antibiotic resistance is ancient and widespread in environmental bacteria. These are therefore reservoirs of resistance elements and reflective of the natural history of antibiotics and resistance. In a previous study, we discovered that multi-drug resistance is common in bacteria isolated from Lechuguilla Cave, an underground ecosystem that has been isolated from the surface for over 4 Myr. Here we use whole-genome sequencing, functional genomics and biochemical assays to reveal the intrinsic resistome of Paenibacillus sp. LC231, a cave bacterial isolate that is resistant to most clinically used antibiotics. We systematically link resistance phenotype to genotype and in doing so, identify 18 chromosomal resistance elements, including five determinants without characterized homologues and three mechanisms not previously shown to be involved in antibiotic resistance. A resistome comparison across related surface Paenibacillus affirms the conservation of resistance over millions of years and establishes the longevity of these genes in this genus.

See more: McMaster Daily News

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genomecanadacolorThe McArthur lab and the Comprehensive Antibiotic Resistance Database are proud to have contributed to the Genome Canada – Canadian Food Inspection Agency Forum on Genomics and Antimicrobial Resistance. The two-day event brought together over sixty leading experts from academic, government, industry and commodities groups to address the challenge of AMR and discuss a path forward. A summary of the Forum and the Workshop Report are now online.

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arjun-at-iidr-trainee-daykirill-usra-poster

Three of our undergraduate students gave poster presentations in the last month. Arjun Sharma (Biochemistry & Biomedical Sciences 3rd year) outlined his work on developing the Comprehensive Antibiotic Resistance Database’s (arpcard.mcmaster.ca) CARD*Shark text mining algorithms at the Michael G. DeGroote Institute for Infectious Disease Research (IIDR) Trainee Day while Kirill Pankov (Biomedical Discovery & Commercialization 4th year) presented the results of his summer NSERC Undergraduate Student Research Award (USRA) research in the Laboratory of Dr. Joanna Wilson into the origin of Cnidarian P450 enzymes, work he is continuing in our lab as part of his thesis research. Mohammad Khan (Biomedical Discovery & Commercialization 4th year), a thesis student in the Laboratory of Dr. Eric Brown that collaborates with our group, also presented a poster at IIDR Trainee Day on his work on chemical-genetic interaction database design.

Sharma, A.N., S. Doshi, A.R. Raphenya, B. Alcock, B.M. Dave, B.A. Lago, K.K. Tsang, & A.G. McArthur. 2016. CARDShark: Computer-assisted biocuration of the Comprehensive Antibiotic Resistance Database. Poster presentation at the 2016 Michael G. DeGroote Institute for Infectious Disease Research (IIDR) Trainee Day, Hamilton, Ontario, Canada.

Pankov, K., A.G. McArthur & J.Y. Wilson. 2016. The Cytochrome P450 (CYP) superfamily in the Cnidarian phylum. Poster presentation at the 2016 Undergraduate Student Research Awards (USRA) Poster Session, Hamilton, Ontario, Canada.

Khan, M.A., S. French, B. Aubie, A.G McArthur & E.D. Brown. 2016. Challenging common screening filters through analysis of a chemical-genetic screening database. Poster presentation at the 2016 Michael G. DeGroote Institute for Infectious Disease Research (IIDR) Trainee Day, Hamilton, Ontario, Canada.

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17-coverNi X, Davis JH, Jain N, Razi A, Benlekbir S, McArthur AG, Rubinstein JL, Britton RA, Williamson JR, Ortega J.

Nucleic Acids Res. 2016 Sep 30;44(17):8442-55.

YphC and YsxC are GTPases in Bacillus subtilis that facilitate the assembly of the 50S ribosomal subunit, however their roles in this process are still uncharacterized. To explore their function, we used strains in which the only copy of the yphC or ysxC genes were under the control of an inducible promoter. Under depletion conditions, they accumulated incomplete ribosomal subunits that we named 45SYphC and 44.5SYsxC particles. Quantitative mass spectrometry analysis and the 5-6 Å resolution cryo-EM maps of the 45SYphC and 44.5SYsxC particles revealed that the two GTPases participate in the maturation of the central protuberance, GTPase associated region and key RNA helices in the A, P and E functional sites of the 50S subunit. We observed that YphC and YsxC bind specifically to the two immature particles, suggesting that they represent either on-pathway intermediates or that their structure has not significantly diverged from that of the actual substrate. These results describe the nature of these immature particles, a widely used tool to study the assembly process of the ribosome. They also provide the first insights into the function of YphC and YsxC in 50S subunit assembly and are consistent with this process occurring through multiple parallel pathways, as it has been described for the 30S subunit.

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genome-canada-1A cross-national research consortia co-led by McMaster’s Andrew McArthur is receiving two of 16 federal grants to further develop a big data solution to the growing problem of antimicrobial resistance (AMR). The government’s investment, totaling more than $4M, is the result of Genome Canada’s 2015 Bioinformatics and Computational Biology Competition, a partnership with the Canadian Institutes of Health Research (CIHR). McArthur and his colleagues will receive $500,000 over two years. McArthur will work closely with researchers from the University of British Columbia, Simon Fraser University, Dalhousie University and the Public Health Agency of Canada to design and develop novel software and database systems that will empower public health agencies and the agri-food sector to rapidly respond to threats posed by infectious disease outbreaks and food-borne illnesses.

Full Coverage: Faculty of Health Sciences, Genome Canada, Newswire, Hamilton Spectator

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Kara Tsang krishna

Kara Tsang (graduate, McMaster BDC) – Kara did her BiomedDC 4A15 thesis in the lab, focused on Pseudomonas resistome prediction and cystic fibrosis-associated metagenomic sequencing and starts September 2016 as MSc student in the area of clinical AMR analytics, particularly metagenomics. Her work will be part of our recently funded Genome Canada grants, as well as part of McMaster’s clinical genome sequencing efforts.

Krishna Srinivasan (graduate, McMaster Biology) – Krishna just finished his undergraduate degree in McMaster’s Biology department, with a thesis in environmental toxicology. He starts as a MSc student September 2016, collaborating with the Jenny lab (UAlabama) on our recently funded NIH grant examining the role of MTF-1 in lens development and cataractogenesis.

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McArthur, A.G.B. Jia, A.R. Raphenya, P. Guo, K. Tsang, B. Dave, B. Alcock, B. Lago, N. Waglechner, & G.D. Wright. 2016. The Comprehensive Antibiotic Resistance Database – A Platform for Antimicrobial Resistance Surveillance. Invited presentation at the 2nd Conference Rapid Microbial NGS and Bioinformatics: Translation Into Practice, Hamburg, Germany.

Antimicrobial resistance (AMR) is among the most pressing public health crises of the 21st Century. Despite the importance of resistance to health, this field has been slow to take advantage of genome scale tools. Phenotype based criteria dominate the epidemiology of antibiotic action and effectiveness. There is a poor understanding of which antibiotic resistance genes are in circulation, which a threat, and how clinicians and public health workers can manage the crisis of resistance. However, DNA sequencing is rapidly decreasing in cost and as such we are on the cusp of an age of high-throughput molecular epidemiology. What are needed are tools for rapid, accurate analysis of DNA sequence data for the genetic underpinnings of antibiotic resistance. In an effort to address this problem, we have created the Comprehensive Antibiotic Resistance Database (card.mcmaster.ca). This database is a rigorously curated collection of known antibiotics, targets, and resistance determinants. It integrates disparate molecular and sequence data, provides a unique organizing principle in the form of the Antibiotic Resistance Ontology (ARO), and can quickly identify putative antibiotic resistance genes in raw genome sequences using the novel Resistance Gene Identifier (RGI). Here we review the current state of the CARD, particularly recent advances in the curation of resistance determinants and the structure of the ARO. We will also present our plans for development of semi- and fully-automated text mining algorithms for curation of broader AMR data, construction of meta-models for improved AMR phenotype prediction, and release of portable command-line genome analysis tools.

 

* presenter underlined, trainees in bold
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briony lago alcockZachary LinKara TsangBiren Davejjiaamospearl
McMaster Interdisciplinary Research Exposition (MIREx); Ontario Biology Day; Biomedical Discovery and Commercialization Engage Symposium; Rapid Microbial NGS and Bioinformatics: Translation Into Practice (Germany); Canadian Food Inspection Agency Forum on Genomics and Antimicrobial Resistance; New Antibacterial Discovery & Development Gordon Research Conference (Italy); McMaster Women in Science and Engineering (WISE) Current Research in Engineering, Science & Technology (CREST) Meeting; 6th Biennial National IDeA Symposium of Biomedical Research Excellence (USA).

Presenter underlined, trainees in bold.

  • Dave, B.M., J.A. Klein, L.A. Knodler, A.R. Raphenya, & A.G. McArthur. 2016. A phylogenetic analysis of Inv/Mxi-Spa proteins and implications for functional complementation. Poster presentation at McMaster Interdisciplinary Research Exposition (MIREx), Hamilton, Ontario, Canada.
  • Dave, B.M., J.A. Klein, L.A. Knodler, A.R. Raphenya, & A.G. McArthur. 2016. A phylogenetic analysis of Inv/Mxi-Spa proteins and implications for functional complementation. Poster presentation at Ontario Biology Day 2016, Toronto, Ontario, Canada.
  • Lin, Z. & A.G. McArthur. 2016. Adapting Galaxy bioinformatics to outbreak-associated Clostridium difficile. Poster presentation at McMaster’s Biomedical Discovery and Commercialization Engage Symposium, Hamilton, Ontario, Canada.
  • McArthur, A.G.B. Jia, A.R. Raphenya, P. Guo, K. Tsang, B. Dave, B. Alcock, B. Lago, N. Waglechner, & G.D. Wright. 2016. The Comprehensive Antibiotic Resistance Database – A Platform for Antimicrobial Resistance Surveillance. Invited presentation at the 2nd Conference Rapid Microbial NGS and Bioinformatics: Translation Into Practice, Hamburg, Germany.
  • McArthur, A.G. 2016. Bioinformatic resources for antimicrobial resistance. Invited presentation at Canadian Food Inspection Agency (CFIA) Forum on Genomics and Antimicrobial Resistance, Ottawa, Ontario, Canada.
  • McArthur, A.G. 2016. Combatting Antibiotic Resistance Using Surveillance. Invited presentation at McMaster Interdisciplinary Research Exposition (MIREx), Hamilton, Ontario, Canada.
  • Pawlowski, A.C., W. Wang, K. Koteva, H.A. Barton, B. Jia, A.R. Raphenya, P. Guo, A.G. McArthur, G.D. Wright. 2016. A multi-antibiotic resistant genotype is maintained for millions of years. Presentation at the New Antibacterial Discovery & Development Gordon Research Conference, Lucca, Italy.
  • Tsang, K. & A.G. McArthur. 2016. Translation of biocuration to metagenomic analysis. Poster presentation at McMaster Interdisciplinary Research Exposition (MIREx), Hamilton, Ontario, Canada.
  • Tsang, K. & A.G. McArthur. 2016. Translation of biocuration to metagenomic analysis. Poster presentation at Ontario Biology Day 2016, Toronto, Ontario, Canada.
  • Tsang, K. & A.G. McArthur. 2016. Translation of biocuration to metagenomic analysis. Poster presentation at McMaster Women in Science and Engineering (WISE) Current Research in Engineering, Science & Technology (CREST) Meeting, Hamilton, Ontario, Canada.
  • Tsang, K. & A.G. McArthur. 2016. Translation of biocuration to metagenomic analysis. Poster presentation at McMaster’s Biomedical Discovery and Commercialization Engage Symposium, Hamilton, Ontario, Canada.
  • Williams, L., A.G. McArthur, B. Lago, A.R. Raphenya, N. Pray, N. Saleem, S. Salas, K. Paulson, R. Mangar, Y. Liu, A. Vo, & J. Shavit. 2016. Nuclear factor, erythoid 2 (Nfe2) is a transcriptional regulator of oxidative stress during zebrafish development. Presentation at the 6th Biennial National IDeA Symposium of Biomedical Research Excellence, Washington, DC.
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