title: The flavanone naringenin reduces the production of quorum sensing-controlled virulence factors in Pseudomonas aeruginosa PAO1.
abstract: Preliminary screening of the Malagasy plant Combretum albiflorum for compounds attenuating the production of quorum sensing (QS)-controlled virulence factors in bacteria led to the identification of active fractions containing flavonoids. In the present study, several flavonoids belonging to the flavone, flavanone, flavonol and chalcone structural groups were screened for their capacity to reduce the production of QS-controlled factors in the opportunistic pathogen Pseudomonas aeruginosa (strain PAO1). Flavanones (i.e. naringenin, eriodictyol and taxifolin) significantly reduced the production of pyocyanin and elastase in P. aeruginosa without affecting bacterial growth. Consistently, naringenin and taxifolin reduced the expression of several QS-controlled genes (i.e. lasI, lasR, rhlI, rhlR, lasA, lasB, phzA1 and rhlA) in P. aeruginosa PAO1. Naringenin also dramatically reduced the production of the acylhomoserine lactones N-(3-oxododecanoyl)-L-homoserine lactone (3-oxo-C12-HSL) and N-butanoyl-L-homoserine lactone (C4-HSL), which is driven by the lasI and rhlI gene products, respectively. In addition, using mutant strains deficient for autoinduction (ΔlasI and ΔrhlI) and LasR- and RhlR-based biosensors, it was shown that QS inhibition by naringenin not only is the consequence of a reduced production of autoinduction compounds but also results from a defect in the proper functioning of the RlhR-C4-HSL complex. Widely distributed in the plant kingdom, flavonoids are known for their numerous and determinant roles in plant physiology, plant development and in the success of plant-rhizobia interactions, but, as shown here, some of them also have a role as inhibitors of the virulence of pathogenic bacteria by interfering with QS mechanisms.
authors.affiliation: Plant Biotechnology Unit, BioVallée, rue Adrienne Bolland 8, B-6041 Gosselies, Belgium.|Laboratoire de Biotechnologie Végétale, Université Libre de Bruxelles, rue des Professeurs Jeener et Brachet 12, B-6041 Gosselies, Belgium.
authors.forename: Olivier M
authors.initials: OM
authors.lastname: Vandeputte
authors.affiliation: Laboratoire de Biochimie et de Chimie Appliquées, Université de Ouagadougou, 09 BP 848 Ouagadougou 09, Burkina Faso.|Laboratoire de Biotechnologie Végétale, Université Libre de Bruxelles, rue des Professeurs Jeener et Brachet 12, B-6041 Gosselies, Belgium.
authors.forename: Martin
authors.initials: M
authors.lastname: Kiendrebeogo
authors.affiliation: Laboratoire de Physiologie Végétale, Université d'Antananarivo, BP 906 Antananarivo 101, Madagascar.
authors.forename: Tsiry
authors.initials: T
authors.lastname: Rasamiravaka
authors.affiliation: Laboratoire de Pharmacognosie, de Bromatologie et de Nutrition Humaine, Université Libre de Bruxelles, CP 205/9, Boulevard du Triomphe, B-1050 Brussels, Belgium.
authors.forename: Caroline
authors.initials: C
authors.lastname: Stévigny
authors.affiliation: Laboratoire de Pharmacognosie, de Bromatologie et de Nutrition Humaine, Université Libre de Bruxelles, CP 205/9, Boulevard du Triomphe, B-1050 Brussels, Belgium.
authors.forename: Pierre
authors.initials: P
authors.lastname: Duez
authors.affiliation: Laboratoire de Physiologie Végétale, Université d'Antananarivo, BP 906 Antananarivo 101, Madagascar.|Laboratoire de Biotechnologie Végétale, Université Libre de Bruxelles, rue des Professeurs Jeener et Brachet 12, B-6041 Gosselies, Belgium.
authors.forename: Sanda
authors.initials: S
authors.lastname: Rajaonson
authors.affiliation: Plant Biotechnology Unit, BioVallée, rue Adrienne Bolland 8, B-6041 Gosselies, Belgium.|Laboratoire de Biotechnologie Végétale, Université Libre de Bruxelles, rue des Professeurs Jeener et Brachet 12, B-6041 Gosselies, Belgium.
authors.forename: Billo
authors.initials: B
authors.lastname: Diallo
authors.affiliation: Laboratoire de Biotechnologie Végétale, Université Libre de Bruxelles, rue des Professeurs Jeener et Brachet 12, B-6041 Gosselies, Belgium.
authors.forename: Adeline
authors.initials: A
authors.lastname: Mol
authors.affiliation: Laboratoire de Biotechnologie Végétale, Université Libre de Bruxelles, rue des Professeurs Jeener et Brachet 12, B-6041 Gosselies, Belgium.
authors.forename: Marie
authors.initials: M
authors.lastname: Baucher
authors.affiliation: Laboratoire de Biotechnologie Végétale, Université Libre de Bruxelles, rue des Professeurs Jeener et Brachet 12, B-6041 Gosselies, Belgium.
authors.forename: Mondher
authors.initials: M
authors.lastname: El Jaziri
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000096:biosynthesis; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D029765:Combretum; D044950:Flavanones / Q000378:metabolism / Q000494:pharmacology*; D005419:Flavonoids / Q000378:metabolism / Q000494:pharmacology; D015964:Gene Expression Regulation, Bacterial; D006714:Homoserine / Q000031:analogs & derivatives / Q000096:biosynthesis; D008025:Ligases / Q000235:genetics; D010196:Pancreatic Elastase / Q000096:biosynthesis; D028321:Plant Preparations / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D011710:Pyocyanine / Q000096:biosynthesis; D053038:Quorum Sensing / Q000235:genetics; D017384:Sequence Deletion; D014157:Transcription Factors / Q000235:genetics; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D044950:Flavanones; D005419:Flavonoids; C081237:LasI protein, Pseudomonas aeruginosa; C109860:N-(3-oxododecanoyl)homoserine lactone; C092312:N-butyrylhomoserine lactone; D028321:Plant Preparations; D014157:Transcription Factors; D037521:Virulence Factors; D006714:Homoserine; D011710:Pyocyanine; D010196:Pancreatic Elastase; D008025:Ligases; C096955:RHLI protein, Pseudomonas aeruginosa; C005273:naringenin; D015107:4-Butyrolactone