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Centre for Biomedical Microbiology, BioCentrum-DTU, Technical University of Denmark, DK-2800 Kgs Lyngby, Denmark
Correspondence
Michael Givskov
immg{at}pop.dtu.dk
Many opportunistic pathogenic bacteria rely on quorum sensing (QS) circuits as central regulators of virulence expression. In Pseudomonas aeruginosa, QS-regulated gene expression contributes to the formation and maintenance of biofilms and their tolerance to conventional antimicrobials and the host innate immune system. Therefore, QS is an obvious target for a novel class of antimicrobial drugs which would function to efficiently block reception of the cognate QS signals in vivo, and thereby be capable of inducing chemical attenuation of pathogens. As QS is not directly involved in processes essential for growth of the bacteria, inhibition of QS does not impose harsh selective pressure for development of resistance as with antibiotics. Numerous chemical libraries of both natural and synthetic origin have been screened and several QS-inhibitory compounds have been identified. In animal pulmonary infection models, such inhibitors have proven able to significantly improve clearing of the infecting bacteria and reduce mortality. In addition, several enzymes that are able to inactivate the bacterial QS signal molecules have been identified. This inactivation leads to blockage of QS-mediated virulence of plant pathogens in several models.
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