Leroi-Gourhan A., Préhistoire. De l'art occidental.

Tannières M.-C. Leroi-Gourhan A., Préhistoire. De l'art occidental.. In: Revue française de sociologie, 1966, 7-4. pp. 536-538

Leroi-Gourhan A., Préhistoire. De l'art occidental.

Tannières M.-C. Leroi-Gourhan A., Préhistoire. De l'art occidental.. In: Revue française de sociologie, 1966, 7-4. pp. 536-538

At a supra-physiological concentration, human sexual hormones act as quorum-sensing inhibitors.

International audienceN-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

Structures of the QSIs identified in the chemical library.

<p>Structures of the QSIs identified in the chemical library.</p

Modeling of interactions between AHL-sensors and human hormones.

<p>Superimposed modeling of the overall binding modes of estradiol (cyan), estriol (magenta), estrone (yellow), or AHLs (OC12-HSL or OC8-HSL in gray) within the binding site of LasR (A) and of TraR (B).Superimposed modeling of the simplified binding modes showing interactions between estradiol (selected as an example in cyan) or natural ligands (OC12-HSL or OC8-HSL in green) and binding sites residues of LasR (C) and TraR (D).</p

Bacterial strains and plasmids used in this study.

<p>Bacterial strains and plasmids used in this study.</p

Structure of the additional QSIs and compounds used in this study.

<p>Structure of the additional QSIs and compounds used in this study.</p

IC50, MIC and MBC values of the tested compounds.

a<p>values are in µg/ml.</p>b<p>In brackets, inhibition (%) at 100 µg/ml.</p

Synthesis of the 4 diastereoisomers of QSI-1248.

<p>Synthesis of the 4 diastereoisomers of QSI-1248.</p