Quorum sensing and the regulation of virulence gene expression in pathogenic bacteria.
For many pathogens, the outcome of the interaction between host and bacterium is strongly affected by the bacterial population size. Coupling the production of virulence factors with cell population density ensures that the mammalian host lacks sufficient time to mount an effective defence against consolidated attack. Such a strategy depends on the ability of an individual bacterial cell to sense other members of the same species and in response, differentially express specific sets of genes. Such cell-cell communication is called "quorum sensing" and involves the direct or indirect activation of a response regulator by a small diffusible signal molecule. A number of chemically distinct quorum-sensing signal molecules have been described including the N-acyl-L-homoserine lactones (AHLs) in Gram-negative bacteria and post-translationally modified peptides in Gram-positive bacteria. For example, the human pathogens Pseudomonas aeruginosa and Staphylococcus aureus employ AHLs and peptides, respectively, to control the expression of multiple virulence genes in concert with cell population density. Apart from their role in signal transduction, certain quorum-sensing signal molecules, notably N-(3-oxododecanoyl)homoserine lactone, possess intrinsic pharmacological and immunomodulatory activities such that they may function as virulence determinants per se. While quorum-sensing signal molecules have been detected in tissues in experimental animal model and human infections, the mutation of genes involved in either quorum-sensing signal generation or signal transduction frequently results in the attenuation of virulence. Thus, interference with quorum sensing represents a promising strategy for the therapeutic or prophylactic control of infection.
Winzer
K
K
Institute of Infections & Immunity, Queen's Medical Centre, University of Nottingham, UK.
Williams
P
P
D015964:Gene Expression Regulation, Bacterial; D006714:Homoserine / Q000031:analogs & derivatives; D006801:Humans; D008163:Luminescent Measurements; D008954:Models, Biological; D010675:Pheromones / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000472:pathogenicity*; D013211:Staphylococcus aureus / Q000235:genetics / Q000472:pathogenicity*; D014774:Virulence / Q000235:genetics
D010675:Pheromones; D006714:Homoserine