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

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.

Geoffrey L. Winsor | Robert E. W. Hancock | Fiona S. L. Brinkman | Ken Dewar | Joe J. Harrison | Luca Freschi | Shawn D. Aaron | Paul B. Rainey | Brian Boyle | Nicholas P. Tucker | Shawn Lewenza | Jérôme Laroche | Lars Jelsbak | Baofeng Jia | Nicholas Waglechner | Sheldon K. Pereira | Andrew G. McArthur | Scott C. Bell | Stephan Heeb | Burkhard Tümmler | Jean-Paul Pirnay | Steve J. Charette | Roger C. Levesque | N. Loman | K. Dewar | G. Winsor | F. Brinkman | J. Jeukens | L. Freschi | I. Kukavica-Ibrulj | N. Tucker | R. Levesque | J. Klockgether | P. Rainey | B. Tümmler | S. Charette | S. Aaron | S. Heeb | A. McArthur | P. Williams | M. Cámara | J. Turton | S. Bell | J. Milot | R. Hancock | A. Cantin | J. Burns | Halim Maaroufi | B. Boyle | J. Laroche | S. Larose | J. Barbeau | J. Fothergill | J. Lam | Gerard D. Wright | F. Malouin | Nicholas Waglechner | Eric Déziel | S. Lewenza | L. Jelsbak | S. Rousseau | D. Nguyen | C. Winstanley | P. Santos | Hardeep Naghra | T. Kidd | K. Grimwood | I. Lamont | Keith Grimwood | Simon Rousseau | Jean Barbeau | G. Perron | Marie-Josée Dupont | M. Moore | J. Harrison | Baofeng Jia | D. Kenna | J. Manos | J. Mckeown | J. Pirnay | A. Stephenson | Véronique L. Taylor | S. Thrane | Julie Jeukens | Irena Kukavica-Ibrulj | Marie-Josée Dupont | Dao Nguyen | Nick Loman | Paul Williams | Iain L. Lamont | Jim Manos | Craig Winstanley | Jens Klockgether | Jane L. Burns | Jane F. Turton | Hardeep Naghra | Stéphane Larose | Julie Milot | Gabriel G. Perron | Éric Déziel | Halim Maaroufi | Joanne L. Fothergill | Matthew Moore | Miguel Camara | André Cantin | Dervla T. Kenna | Timothy J. Kidd | Joseph S. Lam | François Malouin | Josie McKeown | Pedro M. Santos | Anne Stephenson | Véronique Taylor | Sandra W. Thrane | Dao Nguyen | R. Lévesque | J. McKeown | Matthew P. Moore | Julie Jeukens | S. Bell

[1]  A. Goesmann,et al.  Interclonal gradient of virulence in the Pseudomonas aeruginosa pangenome from disease and environment. , 2015, Environmental microbiology.

[2]  Shabhonam Caim,et al.  Draft genomes of 12 host-adapted and environmental isolates of Pseudomonas aeruginosa and their positions in the core genome phylogeny. , 2014, Pathogens and disease.

[3]  J. Jeukens,et al.  Comparative Genomics of Isolates of a Pseudomonas aeruginosa Epidemic Strain Associated with Chronic Lung Infections of Cystic Fibrosis Patients , 2014, PloS one.

[4]  S. McColley,et al.  Clinical Significance of Microbial Infection and Adaptation in Cystic Fibrosis , 2011, Clinical Microbiology Reviews.

[5]  N. Hall,et al.  Genetic Characterization Indicates that a Specific Subpopulation of Pseudomonas aeruginosa Is Associated with Keratitis Infections , 2011, Journal of Clinical Microbiology.

[6]  M. Silby,et al.  Pseudomonas genomes: diverse and adaptable. , 2011, FEMS microbiology reviews.

[7]  A. Vanderkelen,et al.  Pseudomonas aeruginosa displays an epidemic population structure. , 2002, Environmental microbiology.

[8]  B. Ramsey,et al.  Pseudomonas aeruginosa in cystic fibrosis patients with G551D-CFTR treated with ivacaftor. , 2015, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[9]  P. Rainey,et al.  Pseudomonas aeruginosa Exhibits Frequent Recombination, but Only a Limited Association between Genotype and Ecological Setting , 2012, PloS one.

[10]  M. Brockhurst,et al.  Pseudomonas aeruginosa population diversity and turnover in cystic fibrosis chronic infections. , 2011, American journal of respiratory and critical care medicine.

[11]  C. Whitchurch,et al.  Roles of type IV pili, flagellum-mediated motility and extracellular DNA in the formation of mature multicellular structures in Pseudomonas aeruginosa biofilms. , 2008, Environmental microbiology.

[12]  Matthew R. Laird,et al.  IslandViewer 3: more flexible, interactive genomic island discovery, visualization and analysis , 2015, Nucleic Acids Res..

[13]  P. H. Roy,et al.  Complete Genome Sequence of the Multiresistant Taxonomic Outlier Pseudomonas aeruginosa PA7 , 2010, PloS one.

[14]  Gerard D. Wright,et al.  The antibiotic resistance “mobilome”: searching for the link between environment and clinic , 2013, Front. Microbiol..

[15]  J. Emerson,et al.  Pseudomonas aeruginosa and other predictors of mortality and morbidity in young children with cystic fibrosis , 2002, Pediatric pulmonology.

[16]  J. Lyczak,et al.  Establishment of Pseudomonas aeruginosa infection: lessons from a versatile opportunist. , 2000, Microbes and infection.

[17]  Brian D. Ondov,et al.  The Harvest suite for rapid core-genome alignment and visualization of thousands of intraspecific microbial genomes , 2014, Genome Biology.

[18]  S. Lory,et al.  Complete genome sequence of Pseudomonas aeruginosa PAO1, an opportunistic pathogen , 2000, Nature.

[19]  N. Loman,et al.  Clusters of genetically similar isolates of Pseudomonas aeruginosa from multiple hospitals in the UK. , 2013, Journal of medical microbiology.

[20]  Jonathan Crabtree,et al.  Using Sybil for interactive comparative genomics of microbes on the web , 2011, Bioinform..

[21]  Christian Weinel,et al.  Population structure of Pseudomonas aeruginosa , 2007, Proceedings of the National Academy of Sciences.

[22]  Julian Parkhill,et al.  Newly introduced genomic prophage islands are critical determinants of in vivo competitiveness in the Liverpool Epidemic Strain of Pseudomonas aeruginosa. , 2008, Genome research.

[23]  G. A. Whitmore,et al.  A contemporary survival analysis of individuals with cystic fibrosis: a cohort study , 2014, European Respiratory Journal.

[24]  M. Facciotti,et al.  An Integrated Pipeline for de Novo Assembly of Microbial Genomes , 2012, PloS one.

[25]  M. Brockhurst,et al.  Divergent, coexisting Pseudomonas aeruginosa lineages in chronic cystic fibrosis lung infections. , 2015, American journal of respiratory and critical care medicine.

[26]  S. Molin,et al.  Evolutionary insight from whole-genome sequencing of Pseudomonas aeruginosa from cystic fibrosis patients. , 2015, Future microbiology.

[27]  Bruno Pot,et al.  Pseudomonas aeruginosa Population Structure Revisited , 2009, PloS one.

[28]  A. Casadevall,et al.  Microbiology: Ditch the term pathogen , 2014, Nature.

[29]  Robert E W Hancock,et al.  Pseudomonas aeruginosa: new insights into pathogenesis and host defenses. , 2013, Pathogens and disease.

[30]  B. Tümmler,et al.  Sequence Diversity of Pseudomonas aeruginosa: Impact on Population Structure and Genome Evolution , 2000, Journal of bacteriology.

[31]  Paul Stothard,et al.  Comparing thousands of circular genomes using the CGView Comparison Tool , 2012, BMC Genomics.

[32]  Andrew C. Pawlowski,et al.  The Comprehensive Antibiotic Resistance Database , 2013, Antimicrobial Agents and Chemotherapy.

[33]  Li Li,et al.  Genomic analysis reveals that Pseudomonas aeruginosa virulence is combinatorial , 2006, Genome Biology.

[34]  Raymond Lo,et al.  Pseudomonas Genome Database: improved comparative analysis and population genomics capability for Pseudomonas genomes , 2010, Nucleic Acids Res..

[35]  S. Aaron,et al.  A retrospective analysis of biofilm antibiotic susceptibility testing: a better predictor of clinical response in cystic fibrosis exacerbations. , 2009, Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society.

[36]  N. Colegrave,et al.  Harnessing evolutionary biology to combat infectious disease , 2012, Nature Medicine.

[37]  Lutz Wiehlmann,et al.  Pseudomonas aeruginosa Genomic Structure and Diversity , 2011, Front. Microbio..

[38]  Fiona S. L. Brinkman,et al.  IslandViewer: an integrated interface for computational identification and visualization of genomic islands , 2009, Bioinform..

[39]  D. Hughes,et al.  Sampling the Antibiotic Resistome , 2006, Science.

[40]  R. Kassen,et al.  Genome-Wide Patterns of Recombination in the Opportunistic Human Pathogen Pseudomonas aeruginosa , 2014, Genome biology and evolution.

[41]  T.W.R. Lee Eradication of early Pseudomonas infection in cystic fibrosis , 2009, Chronic respiratory disease.

[42]  J. Fothergill,et al.  Impact of Pseudomonas aeruginosa Genomic Instability on the Application of Typing Methods for Chronic Cystic Fibrosis Infections , 2010, Journal of Clinical Microbiology.