title: At a supra-physiological concentration, human sexual hormones act as quorum-sensing inhibitors.
abstract: N-acylhomoserine lactone (AHL)-mediated quorum-sensing (QS) regulates virulence functions in plant and animal pathogens such as Agrobacterium tumefaciens and Pseudomonas aeruginosa. A chemolibrary of more than 3500 compounds was screened using two bacterial AHL-biosensors to identify QS-inhibitors (QSIs). The purity and structure of 15 QSIs selected through this screening were verified using HPLC MS/MS tools and their activity tested on the A. tumefaciens and P. aeruginosa bacterial models. The IC50 value of the identified QSIs ranged from 2.5 to 90 µg/ml, values that are in the same range as those reported for the previously identified QSI 4-nitropyridine-N-oxide (IC50 24 µg/ml). Under the tested culture conditions, most of the identified QSIs did not exhibit bacteriostatic or bactericidal activities. One third of the tested QSIs, including the plant compound hordenine and the human sexual hormone estrone, decreased the frequency of the QS-regulated horizontal transfer of the tumor-inducing (Ti) plasmid in A. tumefaciens. Hordenine, estrone as well as its structural relatives estriol and estradiol, also decreased AHL accumulation and the expression of six QS-regulated genes (lasI, lasR, lasB, rhlI, rhlR, and rhlA) in cultures of the opportunist pathogen P. aeruginosa. Moreover, the ectopic expression of the AHL-receptors RhlR and LasR of P. aeruginosa in E. coli showed that their gene-regulatory activity was affected by the QSIs. Finally, modeling of the structural interactions between the human hormones and AHL-receptors LasR of P. aeruginosa and TraR of A. tumefaciens confirmed the competitive binding capability of the human sexual hormones. This work indicates potential interferences between bacterial and eukaryotic hormonal communications.
authors.affiliation: Institut des Sciences du Végétal (ISV) UPR 2355, Centre National de la Recherche Scientifique, Gif-sur-Yvette, France ; Seeds Innovation Protection Research and Environment (SIPRE), Comité Nord Plants de Pommes de Terre (CNPPT), Achicourt, France.
authors.forename: Amélie
authors.initials: A
authors.lastname: Beury-Cirou
authors.affiliation: Institut des Sciences du Végétal (ISV) UPR 2355, Centre National de la Recherche Scientifique, Gif-sur-Yvette, France.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Tannières
authors.affiliation: Institut de Chimie des Substances Naturelles (ICSN) UPR2301, Centre National de la Recherche Scientifique, Gif-sur-Yvette, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Minard
authors.affiliation: Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS) UMR 5246, INSA Lyon-Université Lyon 1, Villeurbanne, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Soulère
authors.affiliation: Laboratoire de Biotechnologie Végétale, Université Libre de Bruxelles, Gosselies, Belgium.
authors.forename: Tsiry
authors.initials: T
authors.lastname: Rasamiravaka
authors.affiliation: Institut de Chimie des Substances Naturelles (ICSN) UPR2301, Centre National de la Recherche Scientifique, Gif-sur-Yvette, France.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Dodd
authors.affiliation: Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS) UMR 5246, INSA Lyon-Université Lyon 1, Villeurbanne, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Queneau
authors.affiliation: Institut des Sciences du Végétal (ISV) UPR 2355, Centre National de la Recherche Scientifique, Gif-sur-Yvette, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Dessaux
authors.affiliation: Institut de Chimie des Substances Naturelles (ICSN) UPR2301, Centre National de la Recherche Scientifique, Gif-sur-Yvette, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Guillou
authors.affiliation: Laboratoire de Biotechnologie Végétale, Université Libre de Bruxelles, Gosselies, Belgium.
authors.forename: Olivier M
authors.initials: OM
authors.lastname: Vandeputte
authors.affiliation: Institut des Sciences du Végétal (ISV) UPR 2355, Centre National de la Recherche Scientifique, Gif-sur-Yvette, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Faure
mesh_terms: D016960:Agrobacterium tumefaciens / Q000166:cytology / Q000187:drug effects / Q000235:genetics; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D022761:Gene Transfer, Horizontal / Q000187:drug effects; D012739:Gonadal Steroid Hormones / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D010957:Plasmids / Q000235:genetics; D011487:Protein Conformation; D011550:Pseudomonas aeruginosa / Q000166:cytology / Q000187:drug effects; D053038:Quorum Sensing / Q000187:drug effects*; D014439:Tyramine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D001426:Bacterial Proteins; D012739:Gonadal Steroid Hormones; D007211:Indoles; C057812:indoline; C007964:hordenine; D014439:Tyramine