%0 Journal Article
%9 ACL : Articles dans des revues avec comité de lecture répertoriées par l'AERES
%A Hraiech, S.
%A Hiblot, J.
%A Lafleur, J.
%A Lepidi, H.
%A Papazian, L.
%A Rolain, J. M.
%A Raoult, Didier
%A Elias, M.
%A Silby, M. W.
%A Bzdrenga, J.
%A Bregeon, F.
%A Chabriere, E.
%T Inhaled lactonase reduces Pseudomonas aeruginosa quorum sensing and mortality in rat pneumonia
%D 2014
%L PAR00012467
%G ENG
%J Plos One
%@ 1932-6203
%M ISI:000343943100006
%N 10
%P e107125
%R 10.1371/journal.pone.0107125
%U https://www.documentation.ird.fr/hor/PAR00012467
%V 9
%W Horizon (IRD)
%X 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.
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