@article{PAR00012467, title = {{I}nhaled lactonase reduces {P}seudomonas aeruginosa quorum sensing and mortality in rat pneumonia}, author = {{H}raiech, {S}. and {H}iblot, {J}. and {L}afleur, {J}. and {L}epidi, {H}. and {P}apazian, {L}. and {R}olain, {J}. {M}. and {R}aoult, {D}idier and {E}lias, {M}. and {S}ilby, {M}. {W}. and {B}zdrenga, {J}. and {B}regeon, {F}. and {C}habriere, {E}.}, editor = {}, language = {{ENG}}, abstract = {{R}ationale: {T}he effectiveness of antibiotic molecules in treating {P}seudomonas aeruginosa pneumonia is reduced as a result of the dissemination of bacterial resistance. {T}he existence of bacterial communication systems, such as quorum sensing, has provided new opportunities of treatment. {L}actonases efficiently quench acyl-homoserine lactone-based bacterial quorum sensing, implicating these enzymes as potential new anti-{P}seudomonas drugs that might be evaluated in pneumonia. {O}bjectives: {T}he aim of the present study was to evaluate the ability of a lactonase called {S}so{P}ox-{I} to reduce the mortality of a rat {P}. aeruginosa pneumonia. {M}ethods: {T}o assess {S}so{P}ox-{I}-mediated quorum quenching, we first measured the activity of the virulence gene las{B}, the synthesis of pyocianin, the proteolytic activity of a bacterial suspension and the formation of biofilm of a {PAO}1 strain grown in the presence of lactonase. {I}n an acute lethal model of {P}. aeruginosa pneumonia in rats, we evaluated the effects of an early or deferred intra-tracheal treatment with {S}so{P}ox-{I} on the mortality, lung bacterial count and lung damage. {M}easurements and {P}rimary {R}esults: {S}so{P}ox-{I} decreased {PAO}1 las{B} virulence gene activity, pyocianin synthesis, proteolytic activity and biofilm formation. {T}he early use of {S}so{P}ox-{I} reduced the mortality of rats with acute pneumonia from 75% to 20%. {H}istological 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. {C}onclusion: {T}hese results demonstrate the protective effects of lactonase {S}so{P}ox-{I} in {P}. aeruginosa pneumonia and open the way for a future therapeutic use.}, keywords = {}, booktitle = {}, journal = {{P}los {O}ne}, volume = {9}, numero = {10}, pages = {e107125}, ISSN = {1932-6203}, year = {2014}, DOI = {10.1371/journal.pone.0107125}, URL = {https://www.documentation.ird.fr/hor/{PAR}00012467}, }