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 -