title: Inhaled lactonase reduces Pseudomonas aeruginosa quorum sensing and mortality in rat pneumonia.
abstract: BACKGROUND
  The effectiveness of antibiotic molecules in treating Pseudomonas aeruginosa pneumonia is reduced as a result of the dissemination of bacterial resistance. The existence of bacterial communication systems, such as quorum sensing, has provided new opportunities of treatment. Lactonases efficiently quench acyl-homoserine lactone-based bacterial quorum sensing, implicating these enzymes as potential new anti-Pseudomonas drugs that might be evaluated in pneumonia.
  
  
  OBJECTIVE
  The aim of the present study was to evaluate the ability of a lactonase called SsoPox-I to reduce the mortality of a rat P. aeruginosa pneumonia.
  
  
  METHODS
  To assess SsoPox-I-mediated quorum quenching, we first measured the activity of the virulence gene lasB, the synthesis of pyocianin, the proteolytic activity of a bacterial suspension and the formation of biofilm of a PAO1 strain grown in the presence of lactonase. In an acute lethal model of P. aeruginosa pneumonia in rats, we evaluated the effects of an early or deferred intra-tracheal treatment with SsoPox-I on the mortality, lung bacterial count and lung damage.
  SsoPox-I decreased PAO1 lasB virulence gene activity, pyocianin synthesis, proteolytic activity and biofilm formation. The early use of SsoPox-I reduced the mortality of rats with acute pneumonia from 75% to 20%. Histological lung damage was significantly reduced but the lung bacterial count was not modified by the treatment. A delayed treatment was associated with a non-significant reduction of mortality.
  
  
  CONCLUSIONS
  These results demonstrate the protective effects of lactonase SsoPox-I in P. aeruginosa pneumonia and open the way for a future therapeutic use.
authors.affiliation: Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, UMR CNRS-IRD 6236, IFR48, Aix-Marseille Université, Marseille, France; Réanimation - Détresses Respiratoires et Infections Sévères, APHM, CHU Nord, Marseille, France.
authors.forename: Sami
authors.initials: S
authors.lastname: Hraiech
authors.affiliation: Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, UMR CNRS-IRD 6236, IFR48, Aix-Marseille Université, Marseille, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Hiblot
authors.affiliation: Department of Biology, University of Massachusetts Dartmouth, Dartmouth, Massachusetts, United States of America; Department of Emergency Medicine, Alpert School of Medicine, Providence, Rhode Island, United States of America.
authors.forename: John
authors.initials: J
authors.lastname: Lafleur
authors.affiliation: Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, UMR CNRS-IRD 6236, IFR48, Aix-Marseille Université, Marseille, France.
authors.forename: Hubert
authors.initials: H
authors.lastname: Lepidi
authors.affiliation: Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, UMR CNRS-IRD 6236, IFR48, Aix-Marseille Université, Marseille, France; Réanimation - Détresses Respiratoires et Infections Sévères, APHM, CHU Nord, Marseille, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Papazian
authors.affiliation: Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, UMR CNRS-IRD 6236, IFR48, Aix-Marseille Université, Marseille, France.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Rolain
authors.affiliation: Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, UMR CNRS-IRD 6236, IFR48, Aix-Marseille Université, Marseille, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Raoult
authors.affiliation: Weizmann Institute of Science, Biological Chemistry, Rehovot, Israel.
authors.forename: Mikael
authors.initials: M
authors.lastname: Elias
authors.affiliation: Department of Biology, University of Massachusetts Dartmouth, Dartmouth, Massachusetts, United States of America.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Silby
authors.affiliation: Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, UMR CNRS-IRD 6236, IFR48, Aix-Marseille Université, Marseille, France.
authors.forename: Janek
authors.initials: J
authors.lastname: Bzdrenga
authors.affiliation: Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, UMR CNRS-IRD 6236, IFR48, Aix-Marseille Université, Marseille, France.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Bregeon
authors.affiliation: Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, UMR CNRS-IRD 6236, IFR48, Aix-Marseille Université, Marseille, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Chabriere
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D018441:Biofilms / Q000187:drug effects; D002265:Carboxylic Ester Hydrolases / Q000008:administration & dosage*; D004195:Disease Models, Animal; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D008168:Lung / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D008297:Male; D018410:Pneumonia, Bacterial / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000502:physiology*; D053038:Quorum Sensing / Q000187:drug effects*; D051381:Rats; D037521:Virulence Factors / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D037521:Virulence Factors; D002265:Carboxylic Ester Hydrolases