TY - JOUR

T1 - Ajoene, a Sulfur-Rich Molecule from Garlic, Inhibits Genes Controlled by Quorum Sensing

A1 - Jakobsen,Tim Holm

A1 - van Gennip,Maria

A1 - Phipps,Richard Kerry

A1 - Shanmugham,Meenakshi Sundaram

A1 - Christensen,Louise Dahl

A1 - Alhede,Morten

A1 - Skindersoe,Mette Eline

A1 - Rasmussen,Thomas Bovbjerg

A1 - Friedrich,Karlheinz

A1 - Uthe,Friedrich

A1 - Jensen,Peter Østrup

A1 - Moser,Claus Ernst

A1 - Nielsen,Kristian Fog

A1 - Eberl,Leo

A1 - Larsen,Thomas Ostenfeld

A1 - Tanner,David

A1 - Høiby,Niels

A1 - Bjarnsholt,Thomas

A1 - Givskov,Michael

AU - Jakobsen,Tim Holm

AU - van Gennip,Maria

AU - Phipps,Richard Kerry

AU - Shanmugham,Meenakshi Sundaram

AU - Christensen,Louise Dahl

AU - Alhede,Morten

AU - Skindersoe,Mette Eline

AU - Rasmussen,Thomas Bovbjerg

AU - Friedrich,Karlheinz

AU - Uthe,Friedrich

AU - Jensen,Peter Østrup

AU - Moser,Claus Ernst

AU - Nielsen,Kristian Fog

AU - Eberl,Leo

AU - Larsen,Thomas Ostenfeld

AU - Tanner,David

AU - Høiby,Niels

AU - Bjarnsholt,Thomas

AU - Givskov,Michael

PB - American Society for Microbiology

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

U2 - 10.1128/AAC.05919-11

DO - 10.1128/AAC.05919-11

JO - Antimicrobial Agents and Chemotherapy

JF - Antimicrobial Agents and Chemotherapy

SN - 0066-4804

IS - 5

VL - 56

SP - 2314

EP - 2325

ER -