Quorum-sensing blockade as a strategy for enhancing host defences against bacterial pathogens.
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.
Bjarnsholt
Thomas
T
BioScience and Technology, bldg 227, BioCentrum, Technical University of Denmark, 2800 Lyngby, Denmark.
Givskov
Michael
M
D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000276:immunology; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D018441:Biofilms; D003550:Cystic Fibrosis / Q000188:drug therapy / Q000276:immunology / Q000382:microbiology*; D006801:Humans; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000276:immunology / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology*; D053038:Quorum Sensing / Q000187:drug effects* / Q000276:immunology; D014774:Virulence
D000900:Anti-Bacterial Agents; C088386:homoserine lactone; D015107:4-Butyrolactone