Quorum-sensing blockade as a strategy for enhancing host defences against bacterial pathogens

TY - JOUR

T1 - Quorum-sensing blockade as a strategy for enhancing host defences against bacterial pathogens

AU - Bjarnsholt, Thomas

AU - Givskov, Michael

N1 - Keywords: 4-Butyrolactone; Anti-Bacterial Agents; Biofilms; Cystic Fibrosis; Humans; Pseudomonas Infections; Pseudomonas aeruginosa; Quorum Sensing; Virulence

PY - 2007

Y1 - 2007

N2 - Conventional antibiotics target the growth and the basal life processes of bacteria leading to growth arrest and cell death. The selective force that is inherently linked to this mode of action eventually selects out antibiotic-resistant variants. The most obvious alternative to antibiotic-mediated killing or growth inhibition would be to attenuate the bacteria with respect to pathogenicity. The realization that Pseudomonas aeruginosa, and a number of other pathogens, controls much of their virulence arsenal by means of extracellular signal molecules in a process denoted quorum sensing (QS) gave rise to a new 'drug target rush'. Recently, QS has been shown to be involved in the development of tolerance to various antimicrobial treatments and immune modulation. The regulation of virulence via QS confers a strategic advantage over host defences. Consequently, a drug capable of blocking QS is likely to increase the susceptibility of the infecting organism to host defences and its clearance from the host. The use of QS signal blockers to attenuate bacterial pathogenicity, rather than bacterial growth, is therefore highly attractive, particularly with respect to the emergence of multi-antibiotic resistant bacteria.

AB - Conventional antibiotics target the growth and the basal life processes of bacteria leading to growth arrest and cell death. The selective force that is inherently linked to this mode of action eventually selects out antibiotic-resistant variants. The most obvious alternative to antibiotic-mediated killing or growth inhibition would be to attenuate the bacteria with respect to pathogenicity. The realization that Pseudomonas aeruginosa, and a number of other pathogens, controls much of their virulence arsenal by means of extracellular signal molecules in a process denoted quorum sensing (QS) gave rise to a new 'drug target rush'. Recently, QS has been shown to be involved in the development of tolerance to various antimicrobial treatments and immune modulation. The regulation of virulence via QS confers a strategic advantage over host defences. Consequently, a drug capable of blocking QS is likely to increase the susceptibility of the infecting organism to host defences and its clearance from the host. The use of QS signal blockers to attenuate bacterial pathogenicity, rather than bacterial growth, is therefore highly attractive, particularly with respect to the emergence of multi-antibiotic resistant bacteria.

U2 - 10.1098/rstb.2007.2046

DO - 10.1098/rstb.2007.2046

M3 - Journal article

C2 - 17360273

SN - 0962-8436

VL - 362

SP - 1213

EP - 1222

JO - Philosophical Transactions of the Royal Society of London. Biological Sciences

JF - Philosophical Transactions of the Royal Society of London. Biological Sciences

IS - 1483

ER -