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      Clinical utilization of genomics data produced by the international Pseudomonas aeruginosa consortium

      research-article
      1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 2 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 1 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 8 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 16 , 25 , 9 , 26 , 18 , 8 , 27 , 8 , 12 , 28 , 18 , 29 , 30 , 31 , 32 , 12 , 33 , 34 , 23 , 19 , 18 , 8 , 17 , 18 , 3 , 35 , 22 , 2 , 1
      Frontiers in Microbiology
      Frontiers Media S.A.
      Pseudomonas aeruginosa, next-generation sequencing, bacterial genome, phylogeny, database, cystic fibrosis, antibiotic resistance, clinical microbiology

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          Abstract

          The International Pseudomonas aeruginosa Consortium is sequencing over 1000 genomes and building an analysis pipeline for the study of Pseudomonas genome evolution, antibiotic resistance and virulence genes. Metadata, including genomic and phenotypic data for each isolate of the collection, are available through the International Pseudomonas Consortium Database ( http://ipcd.ibis.ulaval.ca/). Here, we present our strategy and the results that emerged from the analysis of the first 389 genomes. With as yet unmatched resolution, our results confirm that P. aeruginosa strains can be divided into three major groups that are further divided into subgroups, some not previously reported in the literature. We also provide the first snapshot of P. aeruginosa strain diversity with respect to antibiotic resistance. Our approach will allow us to draw potential links between environmental strains and those implicated in human and animal infections, understand how patients become infected and how the infection evolves over time as well as identify prognostic markers for better evidence-based decisions on patient care.

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          The comprehensive antibiotic resistance database.

          The field of antibiotic drug discovery and the monitoring of new antibiotic resistance elements have yet to fully exploit the power of the genome revolution. Despite the fact that the first genomes sequenced of free living organisms were those of bacteria, there have been few specialized bioinformatic tools developed to mine the growing amount of genomic data associated with pathogens. In particular, there are few tools to study the genetics and genomics of antibiotic resistance and how it impacts bacterial populations, ecology, and the clinic. We have initiated development of such tools in the form of the Comprehensive Antibiotic Research Database (CARD; http://arpcard.mcmaster.ca). The CARD 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 new unannotated genome sequences. This unique platform provides an informatic tool that bridges antibiotic resistance concerns in health care, agriculture, and the environment.
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            The Harvest suite for rapid core-genome alignment and visualization of thousands of intraspecific microbial genomes

            Whole-genome sequences are now available for many microbial species and clades, however existing whole-genome alignment methods are limited in their ability to perform sequence comparisons of multiple sequences simultaneously. Here we present the Harvest suite of core-genome alignment and visualization tools for the rapid and simultaneous analysis of thousands of intraspecific microbial strains. Harvest includes Parsnp, a fast core-genome multi-aligner, and Gingr, a dynamic visual platform. Together they provide interactive core-genome alignments, variant calls, recombination detection, and phylogenetic trees. Using simulated and real data we demonstrate that our approach exhibits unrivaled speed while maintaining the accuracy of existing methods. The Harvest suite is open-source and freely available from: http://github.com/marbl/harvest. Electronic supplementary material The online version of this article (doi:10.1186/s13059-014-0524-x) contains supplementary material, which is available to authorized users.
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              Sampling the antibiotic resistome.

              Microbial resistance to antibiotics currently spans all known classes of natural and synthetic compounds. It has not only hindered our treatment of infections but also dramatically reshaped drug discovery, yet its origins have not been systematically studied. Soil-dwelling bacteria produce and encounter a myriad of antibiotics, evolving corresponding sensing and evading strategies. They are a reservoir of resistance determinants that can be mobilized into the microbial community. Study of this reservoir could provide an early warning system for future clinically relevant antibiotic resistance mechanisms.
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                Author and article information

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                Journal
                Front Microbiol
                Front Microbiol
                Front. Microbiol.
                Frontiers in Microbiology
                Frontiers Media S.A.
                1664-302X
                29 September 2015
                2015
                : 6
                : 1036
                Affiliations
                [1] 1Institute for Integrative and Systems Biology, Université Laval Quebec, QC, Canada
                [2] 2Institute of Infection and Global Health, University of Liverpool Liverpool, UK
                [3] 3Department of Molecular Biology and Biochemistry, Simon Fraser University Vancouver, BC, Canada
                [4] 4Ottawa Hospital Research Institute Ottawa, ON, Canada
                [5] 5Faculté de Médecine Dentaire, Université de Montréal Montréal, QC, Canada
                [6] 6QIMR Berghofer Medical Research Institute Brisbane, QLD, Australia
                [7] 7Seattle Children's Research Institute, University of Washington School of Medicine Seattle, WA, USA
                [8] 8School of Life Sciences, University of Nottingham Nottingham, UK
                [9] 9Département de Médecine, Université de Sherbrooke Sherbrooke, QC, Canada
                [10] 10Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec Quebec, QC, Canada
                [11] 11Département de Biochimie, de Microbiologie et de Bio-informatique, Faculté des Sciences et de Génie, Université Laval Quebec, QC, Canada
                [12] 12Department of Human Genetics, McGill University Montreal, QC, Canada
                [13] 13INRS Institut Armand Frappier Laval, QC, Canada
                [14] 14School of Medicine, Griffith University Gold Coast, QLD, Australia
                [15] 15Department of Microbiology and Immunology, University of British Columbia Vancouver, BC, Canada
                [16] 16Biological Sciences, University of Calgary Calgary, AB, Canada
                [17] 17Department of Systems Biology, Technical University of Denmark Lyngby, Denmark
                [18] 18M.G. DeGroote Institute for Infectious Disease Research, McMaster University Hamilton, ON, Canada
                [19] 19Antimicrobial Resistance and Healthcare Associated Infections Reference Unit, Public Health England London, UK
                [20] 20Child Health Research Centre, The University of Queensland Brisbane, QLD, Australia
                [21] 21Centre for Infection and Immunity, Queen's University Belfast Belfast, UK
                [22] 22Klinische Forschergruppe, Medizinische Hochschule Hannover, Germany
                [23] 23Department of Molecular and Cellular Biology, University of Guelph Guelph, ON, Canada
                [24] 24Department of Biochemistry, University of Otago Dunedin, New Zealand
                [25] 25Institute for Microbiology and Infection, University of Birmingham Birmingham, UK
                [26] 26Department of Infectious Diseases and Immunology, The University of Sydney Sydney, NSW, Australia
                [27] 27Department of Pneumology, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval Quebec, QC, Canada
                [28] 28Department of Microbiology and Immunology and Department of Experimental Medicine, McGill University Montreal, QC, Canada
                [29] 29Department of Biology, Bard College, Annandale-On-Hudson NY, USA
                [30] 30Laboratory for Molecular and Cellular Technology, Queen Astrid Military Hospital Brussels, Belgium
                [31] 31New Zealand Institute for Advanced Study, Massey University Albany, New Zealand
                [32] 32Max Planck Institute for Evolutionary Biology Plön, Germany
                [33] 33Department of Biology, University of Minho Braga, Portugal
                [34] 34St. Michael's Hospital Toronto, ON, Canada
                [35] 35Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde Glasgow, UK
                Author notes

                Edited by: John R. Battista, Louisiana State University, USA

                Reviewed by: Awdhesh Kalia, University of Texas MD Anderson Cancer Center, USA; Suleyman Yildirim, Istanbu Medipol University International School of Medicine, Turkey

                *Correspondence: Roger C. Levesque, Institute for Integrative and Systems Biology, Université Laval, 1030 Avenue de la Médecine, Quebec, QC G1E 7A9, Canada rclevesq@ 123456ibis.ulaval.ca

                This article was submitted to Evolutionary and Genomic Microbiology, a section of the journal Frontiers in Microbiology

                †These authors have contributed equally to this work.

                Article
                10.3389/fmicb.2015.01036
                4586430
                26483767
                8d5953df-5d67-4137-8b6f-8e9201925a23
                Copyright © 2015 Freschi, Jeukens, Kukavica-Ibrulj, Boyle, Dupont, Laroche, Larose, Maaroufi, Fothergill, Moore, Winsor, Aaron, Barbeau, Bell, Burns, Camara, Cantin, Charette, Dewar, Déziel, Grimwood, Hancock, Harrison, Heeb, Jelsbak, Jia, Kenna, Kidd, Klockgether, Lam, Lamont, Lewenza, Loman, Malouin, Manos, McArthur, McKeown, Milot, Naghra, Nguyen, Pereira, Perron, Pirnay, Rainey, Rousseau, Santos, Stephenson, Taylor, Turton, Waglechner, Williams, Thrane, Wright, Brinkman, Tucker, Tümmler, Winstanley and Levesque.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 13 May 2015
                : 11 September 2015
                Page count
                Figures: 2, Tables: 0, Equations: 0, References: 43, Pages: 8, Words: 5854
                Funding
                Funded by: Cystic Fibrosis Canada 10.13039/501100000082
                Award ID: Grant ID number 2610
                Categories
                Microbiology
                Perspective

                Microbiology & Virology
                pseudomonas aeruginosa,next-generation sequencing,bacterial genome,phylogeny,database,cystic fibrosis,antibiotic resistance,clinical microbiology

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