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Potent and Selective Modulation of the RhlR Quorum Sensing Receptor by Using Non-native Ligands: An Emerging Target for Virulence Control in Pseudomonas aeruginosa.
Eibergen, Nora R; Moore, Joseph D; Mattmann, Margrith E; Blackwell, Helen E.
Afiliación
  • Eibergen NR; Dow Microbial Control, The Dow Chemical Company, 400 Arcola Road, Collegeville, PA, 19426, USA.
  • Moore JD; Dow Microbial Control, The Dow Chemical Company, 400 Arcola Road, Collegeville, PA, 19426, USA.
  • Mattmann ME; Biomatrica, Inc., 5627 Oberlin Drive, Suite 120, San Diego, CA, 92121, USA.
  • Blackwell HE; Department of Chemistry, The University of Wisconsin-Madison, 1101 University Avenue, Madison, WI, 53706, USA. blackwell@chem.wisc.edu.
Chembiochem ; 16(16): 2348-56, 2015 Nov 02.
Article en En | MEDLINE | ID: mdl-26460240
Pseudomonas aeruginosa uses N-acylated L-homoserine lactone signals and a triumvirate of LuxR-type receptor proteins--LasR, RhlR, and QscR--for quorum sensing (QS). Each of these receptors can contribute to QS activation or repression and, thereby, the control of myriad virulence phenotypes in this pathogen. LasR has traditionally been considered to be at the top of the QS receptor hierarchy in P. aeruginosa; however, recent reports suggest that RhlR plays a more prominent role in infection than originally predicted, in some circumstances superseding that of LasR. Herein, we report the characterization of a set of synthetic, small-molecule agonists and antagonists of RhlR. Using E. coli reporter strains, we demonstrated that many of these compounds can selectively activate or inhibit RhlR instead of LasR and QscR. Moreover, several molecules maintain their activities in P. aeruginosa at concentrations analogous to native RhlR signal levels. These compounds represent useful chemical probes to study the role of RhlR in the complex QS circuitry of P. aeruginosa, its direct (and indirect) effects on virulence, and its overall merit as a target for anti-infective therapy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pseudomonas aeruginosa / Proteínas Bacterianas / Virulencia / Percepción de Quorum / Ligandos Idioma: En Revista: Chembiochem Asunto de la revista: BIOQUIMICA Año: 2015 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Alemania

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pseudomonas aeruginosa / Proteínas Bacterianas / Virulencia / Percepción de Quorum / Ligandos Idioma: En Revista: Chembiochem Asunto de la revista: BIOQUIMICA Año: 2015 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Alemania