title: Comparative genomics and biological characterization of sequential Pseudomonas aeruginosa isolates from persistent airways infection.
abstract: BACKGROUND
  Pseudomonas aeruginosa establishes life-long chronic airway infections in cystic fibrosis (CF) patients. As the disease progresses, P. aeruginosa pathoadaptive variants are distinguished from the initially acquired strain. However, the genetic basis and the biology of host-bacteria interactions leading to a persistent lifestyle of P. aeruginosa are not understood. As a model system to study long term and persistent CF infections, the P. aeruginosa RP73, isolated 16.9 years after the onset of airways colonization from a CF patient, was investigated. Comparisons with strains RP1, isolated at the onset of the colonization, and clonal RP45, isolated 7 years before RP73 were carried out to better characterize genomic evolution of P. aeruginosa in the context of CF pathogenicity.
  
  
  RESULTS
  Virulence assessments in disease animal model, genome sequencing and comparative genomics analysis were performed for clinical RP73, RP45, RP1 and prototype strains. In murine model, RP73 showed lower lethality and a remarkable capability of long-term persistence in chronic airways infection when compared to other strains. Pathological analysis of murine lungs confirmed advanced chronic pulmonary disease, inflammation and mucus secretory cells hyperplasia. Genomic analysis predicted twelve genomic islands in the RP73 genome, some of which distinguished RP73 from other prototype strains and corresponded to regions of genome plasticity. Further, comparative genomic analyses with sequential RP isolates showed signatures of pathoadaptive mutations in virulence factors potentially linked to the development of chronic infections in CF.
  
  
  CONCLUSIONS
  The genome plasticity of P. aeruginosa particularly in the RP73 strain strongly indicated that these alterations may form the genetic basis defining host-bacteria interactions leading to a persistent lifestyle in human lungs.
authors.affiliation: Infections and Cystic Fibrosis Unit, Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, Milano, Italy. bianconi.irene@hsr.it.
authors.forename: Irene
authors.initials: I
authors.lastname: Bianconi
authors.affiliation: Institut de biologie intégrative et des systèmes (IBIS), Université Laval, Quebec, Canada. julie.jeukens.1@ulaval.ca.
authors.forename: Julie
authors.initials: J
authors.lastname: Jeukens
authors.affiliation: Institut de biologie intégrative et des systèmes (IBIS), Université Laval, Quebec, Canada. luca.freschi@bio.ulaval.ca.
authors.forename: Luca
authors.initials: L
authors.lastname: Freschi
authors.affiliation: Infections and Cystic Fibrosis Unit, Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, Milano, Italy. alcalafranco.beatriz@hsr.it.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Alcalá-Franco
authors.affiliation: Infections and Cystic Fibrosis Unit, Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, Milano, Italy. facchini.marcella@hsr.it.
authors.forename: Marcella
authors.initials: M
authors.lastname: Facchini
authors.affiliation: Institut de biologie intégrative et des systèmes (IBIS), Université Laval, Quebec, Canada. Brian.Boyle@ibis.ulaval.ca.
authors.forename: Brian
authors.initials: B
authors.lastname: Boyle
authors.affiliation: Università di Napoli Federico II, Napoli, Italy. molinaro@unina.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: Molinaro
authors.affiliation: Institut de biologie intégrative et des systèmes (IBIS), Université Laval, Quebec, Canada. kukavica@fmed.ulaval.ca.
authors.forename: Irena
authors.initials: I
authors.lastname: Kukavica-Ibrulj
authors.affiliation: Medizinische Hochschule Hannover, Hannover, Germany. Tuemmler.Burkhard@mh-hannover.de.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Tümmler
authors.affiliation: Institut de biologie intégrative et des systèmes (IBIS), Université Laval, Quebec, Canada. rclevesq@ibis.ulaval.ca.
authors.forename: Roger C
authors.initials: RC
authors.lastname: Levesque
authors.affiliation: Infections and Cystic Fibrosis Unit, Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, Milano, Italy. bragonzi.alessandra@hsr.it.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bragonzi
mesh_terms: D000818:Animals; D003550:Cystic Fibrosis / Q000382:microbiology*; D004195:Disease Models, Animal; D016680:Genome, Bacterial / Q000235:genetics*; D023281:Genomics; D007249:Inflammation / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000502:physiology*; D012141:Respiratory Tract Infections / Q000378:metabolism / Q000382:microbiology; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D037521:Virulence Factors