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: Rodolfo García-Contreras, Berenice Peréz-Eretza, Ricardo Jasso-Chávez, Elizabeth Lira-Silva, Jesús Alberto Roldán-Sánchez, Abigail González-Valdez, Gloria Soberón-Chávez, Rafael Coria-Jiménez, Mariano Martínez-Vázquez, Luis David Alcaraz, Toshinari Maeda, Thomas K Wood
• Journal: Pathogens and disease (Pathog Dis) Vol. 73 Issue 6 Pg. ftv040 (Aug 2015) ISSN: 2049-632X [Electronic] United States
• PMID: 26048733 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: © FEMS 2015. All rights reserved. For permissions, please e-mail: [email protected].

Chemical References

• Anti-Bacterial Agents
• Furans
• Virulence Factors
• furanone C-30
• Pyocyanine
• Pancreatic Elastase

Topics

• Anti-Bacterial Agents (metabolism)
• Cystic Fibrosis (complications)
• Down-Regulation
• Drug Resistance, Bacterial
• Furans (metabolism)
• Gene Expression Regulation, Bacterial (drug effects)
• Humans
• Mutation
• Pancreatic Elastase (biosynthesis)
• Permeability
• Pseudomonas Infections (microbiology)
• Pseudomonas aeruginosa (drug effects, growth & development, isolation & purification, physiology)
• Pyocyanine (biosynthesis)
• Quorum Sensing
• Respiratory Tract Infections (microbiology)
• Virulence Factors (biosynthesis)