Ajoene, a Sulfur-Rich Molecule from Garlic, Inhibits Genes Controlled by Quorum Sensing
Top Cited Papers
Open Access
- 1 May 2012
- journal article
- research article
- Published by American Society for Microbiology in Antimicrobial Agents and Chemotherapy
- Vol. 56 (5), 2314-2325
- https://doi.org/10.1128/aac.05919-11
Abstract
In relation to emerging multiresistant bacteria, development of antimicrobials and new treatment strategies of infections should be expected to become a high-priority research area. Quorum sensing (QS), a communication system used by pathogenic bacteria like Pseudomonas aeruginosa to synchronize the expression of specific genes involved in pathogenicity, is a possible drug target. Previous in vitro and in vivo studies revealed a significant inhibition of P. aeruginosa QS by crude garlic extract. By bioassay-guided fractionation of garlic extracts, we determined the primary QS inhibitor present in garlic to be ajoene, a sulfur-containing compound with potential as an antipathogenic drug. By comprehensive in vitro and in vivo studies, the effect of synthetic ajoene toward P. aeruginosa was elucidated. DNA microarray studies of ajoene-treated P. aeruginosa cultures revealed a concentration-dependent attenuation of a few but central QS-controlled virulence factors, including rhamnolipid. Furthermore, ajoene treatment of in vitro biofilms demonstrated a clear synergistic, antimicrobial effect with tobramycin on biofilm killing and a cease in lytic necrosis of polymorphonuclear leukocytes. Furthermore, in a mouse model of pulmonary infection, a significant clearing of infecting P. aeruginosa was detected in ajoene-treated mice compared to a nontreated control group. This study adds to the list of examples demonstrating the potential of QS-interfering compounds in the treatment of bacterial infections.Keywords
This publication has 81 references indexed in Scilit:
- Quorum Sensing Inhibitors Increase the Susceptibility of Bacterial Biofilms to Antibiotics In Vitro and In VivoAntimicrobial Agents and Chemotherapy, 2011
- Quorum Sensing and Virulence of Pseudomonas aeruginosa during Lung Infection of Cystic Fibrosis PatientsPLOS ONE, 2010
- Nonrandom Distribution of Pseudomonas aeruginosa and Staphylococcus aureus in Chronic WoundsJournal of Clinical Microbiology, 2009
- Pseudomonas aeruginosa recognizes and responds aggressively to the presence of polymorphonuclear leukocytesMicrobiology, 2009
- Inactivation of the rhlA gene in Pseudomonas aeruginosa prevents rhamnolipid production, disabling the protection against polymorphonuclear leukocytesAPMIS, 2009
- Computer-Aided Identification of Recognized Drugs as Pseudomonas aeruginosa Quorum-Sensing InhibitorsAntimicrobial Agents and Chemotherapy, 2009
- Novel experimental Pseudomonas aeruginosa lung infection model mimicking long‐term host–pathogen interactions in cystic fibrosisAPMIS, 2009
- Why chronic wounds will not heal: a novel hypothesisWound Repair and Regeneration, 2007
- Multiple Roles of Biosurfactants in Structural Biofilm Development by Pseudomonas aeruginosaJournal of Bacteriology, 2007
- http://www.cdc.gov/ncidod/eid/vol4no4/vandelden.htmEmerging Infectious Diseases, 1998