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Growth inhibition of adherent Pseudomonas aeruginosa by an N-butanoyl-l-homoserine lactone analog

Khalilzadeh, Pouneh; Lajoie, Barbora; El Hage, Salom�; Furiga, Aur�lie; Baziard, Genevi�ve; Berge, Mathieu; Roques, Christine
April 2010
Canadian Journal of Microbiology;Apr2010, Vol. 56 Issue 4, p317
Academic Journal
The discovery of quorum sensing (QS) communication systems regulating bacterial virulence has afforded a novel opportunity for controlling infectious bacteria by interfering with QS. Pseudomonas aeruginosa is an example of an opportunistic human pathogen for which N-acyl homoserine lactone (AHL)-related compounds have been described as potent inhibitors of biofilm formation and virulence factors, given their similarity to the natural QS autoinducers (AHLs). Our purpose was to design potent analogs of N-butanoyl-l-homoserine lactone (C4-HSL) and to screen them for biological activity. Eleven original compounds characterized by the modification of the lactone moiety were screened for their ability to impair biofilm formation. Among them, compound 11 was able to modify the growth kinetics and to restrict the number of adherent cells when added from the early stages of biofilm formation (i.e., adhesion and microcolony formation) in a dose-dependent manner. To demonstrate antagonism with C4-HSL, we showed that the inhibition of biofilm formation by compound 11 was impaired when C4-HSL was added. Structure-activity relationships are discussed with respect to the results obtained. La d�couverte du quorum sensing (QS), syst�me de communication r�gulant la virulence bact�rienne, permet une nouvelle approche dans le contr�le des infections bact�riennes en interf�rant avec ce syst�me. Pseudomonas aeruginosa est un exemple de bact�rie pathog�ne opportuniste pour laquelle les compos�s de type N-acyl homos�rine lactones (AHLs) ont �t� d�crits comme des inhibiteurs potentiels de la formation de biofilm et de l�expression des facteurs de virulence, compte tenu de leur similitude avec les auto-inducteurs naturels impliqu�s dans le QS. Notre objectif �tait de concevoir des analogues de la N-butanoyl-l-homos�rine lactone (C4-HSL) et de les cribler pour leur activit� biologique. Onze analogues originaux, caract�ris�s par des modifications du cycle lactone, ont �t� synth�tis�s puis �valu�s pour leur capacit� � inhiber la formation du biofilm. Parmi ces analogues, le compos� 11 induit des modifications de la cin�tique de formation du biofilm et r�duit le nombre de cellules adh�r�es s�il est pr�sent d�s les premi�res �tapes de formation du biofilm (adh�sion et formation des micro-colonies); l�effet observ� est d�pendant de la dose. Afin de confirmer l�antagonisme avec la C4-HSL, nous avons montr� que l�inhibition de la formation du biofilm par le compos� 11 �tait r�duite lors de l�addition conjointe de la C4-HSL. Pour finir, les relations structure-activit� sont discut�es en fonction des r�sultats obtenus.



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