title: Metabolic pathways of Pseudomonas aeruginosa involved in competition with respiratory bacterial pathogens.
abstract: BACKGROUND
  Chronic airway infection by Pseudomonas aeruginosa considerably contributes to lung tissue destruction and impairment of pulmonary function in cystic-fibrosis (CF) patients. Complex interplays between P. aeruginosa and other co-colonizing pathogens including Staphylococcus aureus, Burkholderia sp., and Klebsiella pneumoniae may be crucial for pathogenesis and disease progression.
  
  
  METHODS
  We generated a library of PA14 transposon insertion mutants to identify P. aeruginosa genes required for exploitative and direct competitions with S. aureus, Burkholderia cenocepacia, and K. pneumoniae.
  
  
  RESULTS
  Whereas wild-type PA14 inhibited S. aureus growth, two transposon insertions located in pqsC and carB, resulted in reduced growth inhibition. PqsC is involved in the synthesis of 4-hydroxy-2-alkylquinolines (HAQs), a family of molecules having antibacterial properties, while carB is a key gene in pyrimidine biosynthesis. The carB mutant was also unable to grow in the presence of B. cepacia and K. pneumoniae but not Escherichia coli and S. epidermidis. We further identified a transposon insertion in purF, encoding a key enzyme of purine metabolism. This mutant displayed a severe growth deficiency in the presence of Gram-negative but not of Gram-positive bacteria. We identified a beneficial interaction in a bioA transposon mutant, unable to grow on rich medium. This growth defect could be restored either by addition of biotin or by co-culturing the mutant in the presence of K. pneumoniae or E. coli.
  
  
  CONCLUSIONS
  Complex interactions take place between the various bacterial species colonizing CF-lungs. This work identified both detrimental and beneficial interactions occurring between P. aeruginosa and three other respiratory pathogens involving several major metabolic pathways. Manipulating these pathways could be used to interfere with bacterial interactions and influence the colonization by respiratory pathogens.
authors.affiliation: Service of Infectious Diseases, Department of Medical Specialities, University Hospitals Geneva Geneva, Switzerland ; Department of Microbiology and Molecular Medicine, University of Geneva Geneva, Switzerland.
authors.forename: Marie
authors.initials: M
authors.lastname: Beaume
authors.affiliation: Service of Infectious Diseases, Department of Medical Specialities, University Hospitals Geneva Geneva, Switzerland ; Department of Microbiology and Molecular Medicine, University of Geneva Geneva, Switzerland.
authors.forename: Thilo
authors.initials: T
authors.lastname: Köhler
authors.affiliation: Service of Infectious Diseases, Department of Medical Specialities, University Hospitals Geneva Geneva, Switzerland ; Department of Microbiology and Molecular Medicine, University of Geneva Geneva, Switzerland.
authors.forename: Thierry
authors.initials: T
authors.lastname: Fontana
authors.affiliation: Service of Infectious Diseases, Department of Medical Specialities, University Hospitals Geneva Geneva, Switzerland ; Department of Microbiology and Molecular Medicine, University of Geneva Geneva, Switzerland.
authors.forename: Mikael
authors.initials: M
authors.lastname: Tognon
authors.affiliation: Service of Infectious Diseases, Department of Medical Specialities, University Hospitals Geneva Geneva, Switzerland.
authors.forename: Adriana
authors.initials: A
authors.lastname: Renzoni
authors.affiliation: Service of Infectious Diseases, Department of Medical Specialities, University Hospitals Geneva Geneva, Switzerland ; Department of Microbiology and Molecular Medicine, University of Geneva Geneva, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: van Delden
keywords: Pseudomonas aeruginosa; Staphylococcus aureus; beneficial interactions; direct competition; exploitative competition; respiratory pathogens