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

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

Author information

1
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.
2
Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, UMR CNRS-IRD 6236, IFR48, Aix-Marseille Université, Marseille, France.
3
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.
4
Weizmann Institute of Science, Biological Chemistry, Rehovot, Israel.
5
Department of Biology, University of Massachusetts Dartmouth, Dartmouth, Massachusetts, United States of America.

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.

PMID:
25350373
PMCID:
PMC4211673
DOI:
10.1371/journal.pone.0107125
[Indexed for MEDLINE]
Free PMC Article

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