Inhaled lactonase reduces Pseudomonas aeruginosa quorum sensing and mortality in rat pneumonia

PLoS One. 2014 Oct 28;9(10):e107125. doi: 10.1371/journal.pone.0107125. eCollection 2014.

Abstract

Rationale: 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.

Objectives: 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.

Measurements and primary results: 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.

Conclusion: These results demonstrate the protective effects of lactonase SsoPox-I in P. aeruginosa pneumonia and open the way for a future therapeutic use.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Animals
  • Anti-Bacterial Agents / administration & dosage*
  • Biofilms / drug effects
  • Carboxylic Ester Hydrolases / administration & dosage*
  • Disease Models, Animal
  • Gene Expression Regulation, Bacterial / drug effects
  • Lung / drug effects
  • Lung / microbiology
  • Lung / pathology
  • Male
  • Pneumonia, Bacterial / drug therapy*
  • Pneumonia, Bacterial / mortality*
  • Pneumonia, Bacterial / pathology
  • Pseudomonas Infections / drug therapy*
  • Pseudomonas Infections / mortality*
  • Pseudomonas Infections / pathology
  • Pseudomonas aeruginosa / physiology*
  • Quorum Sensing / drug effects*
  • Rats
  • Virulence Factors / genetics

Substances

  • Anti-Bacterial Agents
  • Virulence Factors
  • Carboxylic Ester Hydrolases

Grant support

This study was funded by Aix Marseille University (AMU) and had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.