title: Phenotypic shift in Pseudomonas aeruginosa populations from cystic fibrosis lungs after 2-week antipseudomonal treatment.
abstract: BACKGROUND
  The influence of suppressive therapy on the different P. aeruginosa phenotypes harbored in the lungs of cystic fibrosis (CF) patients remains unclear. Our aim was to investigate the phenotypic changes (mucoidy, hypermutability, antibiotic resistance, transcriptomic profiles and biofilm) in P. aeruginosa populations before and after a 2-week course of suppressive antimicrobial therapy in chronically infected CF patients in Denmark.
  
  
  METHODS
  Prospective observational clinical study. Sputum samples were assessed before and after treatment for P. aeruginosa, with regard to: a) colony-forming units (CFU/mL), b) frequency of mucoids and non-mucoids, c) resistance pattern to anti-pseudomonal drugs, d) hypermutability, e) transcriptomic profiles, and f) presence of biofilms.
  
  
  RESULTS
  We collected 23 sputum samples (12 before antibiotic treatment and 11 after) and 77 P. aeruginosa from different CF patients. After treatment, the P. aeruginosa burden diminished but antimicrobial resistance to aztreonam, tobramycin and ceftazidime rose; non-mucoid phenotypes presented increased resistance to colistin, tobramycin, meropenem, and ciprofloxacin, and hypermutable phenotypes to ciprofloxacin. In spite of biofilm persistence, a down-regulation of genes involved in denitrification was detected.
  
  
  CONCLUSIONS
  A 2-week course of suppressive therapy reduces P. aeruginosa lung colonization and influences nitrogen metabolism genes, but also promotes antimicrobial resistance while P. aeruginosa persists in biofilms.
authors.affiliation: Centro de Investigación Biomedica En Red-Enfermedades Respiratorias (CibeRes, CB06/06/0028), Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), CELLEX Laboratories, School of Medicine, University of Barcelona, Spain. Electronic address: lfernan1@clinic.ub.es.
authors.forename: Laia
authors.initials: L
authors.lastname: Fernández-Barat
authors.affiliation: Department of Immunology and Microbiology, Costerton Biofilm Center, Copenhagen, Denmark; Department of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Oana
authors.initials: O
authors.lastname: Ciofu
authors.affiliation: Department of Immunology and Microbiology, Costerton Biofilm Center, Copenhagen, Denmark; Department of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Kasper N
authors.initials: KN
authors.lastname: Kragh
authors.affiliation: Department of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark; CF Center, Rigshospitalet, Denmark.
authors.forename: Tania
authors.initials: T
authors.lastname: Pressler
authors.affiliation: Department of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Ulla
authors.initials: U
authors.lastname: Johansen
authors.affiliation: Centro de Investigación Biomedica En Red-Enfermedades Respiratorias (CibeRes, CB06/06/0028), Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), CELLEX Laboratories, School of Medicine, University of Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Motos
authors.affiliation: Centro de Investigación Biomedica En Red-Enfermedades Respiratorias (CibeRes, CB06/06/0028), Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), CELLEX Laboratories, School of Medicine, University of Barcelona, Spain; Pneumology Service, Clinical Thorax Institute, Hospital Clinic, Barcelona, Spain.
authors.forename: Antoni
authors.initials: A
authors.lastname: Torres
authors.affiliation: Department of Immunology and Microbiology, Costerton Biofilm Center, Copenhagen, Denmark; Department of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Hoiby
mesh_terms: D000890:Anti-Infective Agents / Q000145:classification / Q000627:therapeutic use; D018441:Biofilms / Q000187:drug effects; D003550:Cystic Fibrosis / Q000150:complications / Q000453:epidemiology / Q000382:microbiology; D003718:Denmark / Q000453:epidemiology; D004352:Drug Resistance, Microbial; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000379:methods; D011552:Pseudomonas Infections / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology; D012141:Respiratory Tract Infections / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology*; D013183:Sputum / Q000382:microbiology
chemical_list: D000890:Anti-Infective Agents
keywords: Bacterial infection; Biofilm; Cystic fibrosis; Pseudomonas aeruginosa; Respiratory infection