Quorum sensing: an emerging target for antibacterial chemotherapy?
The emergence of bacterial strains exhibiting resistance to multiple antibiotic classes poses a major threat to medicine and public health. This has been compounded over the last few decades by the failure of drug discovery programmes to provide new broad spectrum antibacterials with novel modes of action. As a consequence, there is renewed interest in antibacterial targets which disrupt the capacity of pathogenic bacteria to cause infection by attenuating virulence. In this respect, one crucial feature of almost all bacterial infections is that the pathogen must attain a critical cell population density sufficient to overwhelm the host defences. Many pathogens are now known to regulate diverse physiological processes, including virulence, in a cell density dependent manner through cell-cell communication. This phenomenon, which relies upon the interaction of a diffusible signal molecule with a sensor kinase or response regulator, has become known as 'quorum sensing'. This review considers the molecular basis of quorum sensing and whether it constitutes a potential therapeutic target for the design of small molecule antagonists capable of controlling infection by attenuating adaptation to the host environment.
Williams
Paul
P
Institute of Infections and Immunity, University of Nottingham, Queen's Medical Centre, Nottingham, NG7 2UH UK. paul.williams@nottingham.ac.uk
D015107:4-Butyrolactone / Q000031:analogs & derivatives; D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001424:Bacterial Infections / Q000188:drug therapy; D018407:Bacterial Physiological Phenomena / Q000187:drug effects*; D001426:Bacterial Proteins / Q000502:physiology; D013437:Carbon-Sulfur Lyases; D004058:Diffusion; D015195:Drug Design; D004351:Drug Resistance; D005656:Fungal Proteins; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects / Q000502:physiology; D006360:Heat-Shock Proteins; D006714:Homoserine / Q000031:analogs & derivatives / Q000502:physiology; D006801:Humans; D007783:Lactones / Q000378:metabolism; D008025:Ligases; D008969:Molecular Sequence Data; D011156:Population Density; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000502:physiology; D012097:Repressor Proteins / Q000502:physiology; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000187:drug effects; D013210:Staphylococcus / Q000187:drug effects / Q000502:physiology; D015534:Trans-Activators / Q000502:physiology; D014733:Vibrio / Q000187:drug effects / Q000502:physiology; D014774:Virulence / Q000187:drug effects / Q000502:physiology
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D005656:Fungal Proteins; D006360:Heat-Shock Proteins; D007783:Lactones; C091088:N-octanoylhomoserine lactone; D012097:Repressor Proteins; D015534:Trans-Activators; C064778:LuxR autoinducer binding proteins; D006714:Homoserine; D013437:Carbon-Sulfur Lyases; C117753:LuxS protein, Bacteria; D008025:Ligases; C449816:N-acylhomoserine lactone synthase; D015107:4-Butyrolactone