title: Growth inhibition of adherent Pseudomonas aeruginosa by an N-butanoyl-L-homoserine lactone analog.
abstract: 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.
authors.affiliation: LU49, Adhesion bacterienne et formation de biofilms, Universite Paul Sabatier, Universite de Toulouse III, Toulouse, France.
authors.forename: Pouneh
authors.initials: P
authors.lastname: Khalilzadeh
authors.forename: Barbora
authors.initials: B
authors.lastname: Lajoie
authors.forename: Salomé
authors.initials: S
authors.lastname: El Hage
authors.forename: Aurélie
authors.initials: A
authors.lastname: Furiga
authors.forename: Geneviève
authors.initials: G
authors.lastname: Baziard
authors.forename: Mathieu
authors.initials: M
authors.lastname: Berge
authors.forename: Christine
authors.initials: C
authors.lastname: Roques
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006801:Humans; D011552:Pseudomonas Infections / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000502:physiology*; D053038:Quorum Sensing / Q000187:drug effects; D013329:Structure-Activity Relationship; D037521:Virulence Factors
chemical_list: D000900:Anti-Bacterial Agents; C092312:N-butyrylhomoserine lactone; D037521:Virulence Factors; D015107:4-Butyrolactone