title: High variability in quorum quenching and growth inhibition by furanone C-30 in Pseudomonas aeruginosa clinical isolates from cystic fibrosis patients.
abstract: Pseudomonas aeruginosa colonizes the lungs of cystic fibrosis patients causing severe damage. This bacterium is intrinsically resistant to antibiotics and shows resistance against new antimicrobials and its virulence is controlled by the quorum-sensing response. Thus, attenuating its virulence by quorum quenching instead of inhibiting its growth has been proposed to minimize resistance; however, resistance against the canonical quorum quencher furanone C-30 can be achieved by mutations leading to increased efflux. In the present work, the effect of C-30 in the attenuation of the QS-controlled virulence factors elastase and pyocyanin was investigated in 50 isolates from cystic fibrosis patients. The results demonstrate that there is a high variability in the expression of both elastase and pyocyanin and that there are many naturally resistant C-30 strains. We report that the main mechanism of C-30 resistance in these strains was not due to enhanced efflux but a lack of permeability. Moreover, C-30 strongly inhibited the growth of several of the isolates studied, thus imposing high selective pressure for the generation of resistance.
authors.affiliation: Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México, 04510 México Departamento de Bioquímica, Instituto Nacional de Cardiología, Mexico City 14080, Mexico rgarc@bq.unam.mx.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: García-Contreras
authors.affiliation: Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México, 04510 México.
authors.forename: Berenice
authors.initials: B
authors.lastname: Peréz-Eretza
authors.affiliation: Departamento de Bioquímica, Instituto Nacional de Cardiología, Mexico City 14080, Mexico.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Jasso-Chávez
authors.affiliation: Departamento de Bioquímica, Instituto Nacional de Cardiología, Mexico City 14080, Mexico.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Lira-Silva
authors.affiliation: Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México, 04510 México.
authors.forename: Jesús Alberto
authors.initials: JA
authors.lastname: Roldán-Sánchez
authors.affiliation: Departamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, 04510 México.
authors.forename: Abigail
authors.initials: A
authors.lastname: González-Valdez
authors.affiliation: Departamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, 04510 México.
authors.forename: Gloria
authors.initials: G
authors.lastname: Soberón-Chávez
authors.affiliation: Laboratory of Experimental Bacteriology, National Institute of Pediatrics, Mexico City 04530, Mexico.
authors.forename: Rafael
authors.initials: R
authors.lastname: Coria-Jiménez
authors.affiliation: Institute of Chemistry, National Autonomous University of Mexico, 04510 Mexico.
authors.forename: Mariano
authors.initials: M
authors.lastname: Martínez-Vázquez
authors.affiliation: Departamento de Ecología de la Biodiversidad, Instituto de Ecología, Universidad Nacional Autónoma de México, 04510 México.
authors.forename: Luis David
authors.initials: LD
authors.lastname: Alcaraz
authors.affiliation: Department of Biological Functions and Engineering, Kyushu Institute of Technology, Kitakyushu 808-0196, Japan.
authors.forename: Toshinari
authors.initials: T
authors.lastname: Maeda
authors.affiliation: Departments of Chemical Engineering and Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA 16802-4400, USA.
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Wood
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism*; D003550:Cystic Fibrosis / Q000150:complications; D015536:Down-Regulation; D024881:Drug Resistance, Bacterial; D005663:Furans / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects*; D006801:Humans; D009154:Mutation; D010196:Pancreatic Elastase / Q000096:biosynthesis; D010539:Permeability; D011552:Pseudomonas Infections / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000254:growth & development / Q000302:isolation & purification / Q000502:physiology; D011710:Pyocyanine / Q000096:biosynthesis; D053038:Quorum Sensing; D012141:Respiratory Tract Infections / Q000382:microbiology*; D037521:Virulence Factors / Q000096:biosynthesis
chemical_list: D000900:Anti-Bacterial Agents; D005663:Furans; D037521:Virulence Factors; C494198:furanone C-30; D011710:Pyocyanine; D010196:Pancreatic Elastase
keywords: Pseudomonas aeruginosa; clinical isolates; quorum quenching; resistance; virulence factors