Quorum sensing and the population-dependent control of virulence

One crucial feature of almost all bacterial infections is the need for the invading pathogen to reach a critical cell population density sufficient to overcome host defences and establish the infection. Controlling the expres sion of virulence determinants in concert with cell population density may therefore confer a significant survival advantage on the pathogen such that the host is overwhelmed before a defence response can be fully initiated. Many different bacterial pathogens are now known to regulate diverse physio logical processes including virulence in a cell-density-dependent manner th rough cell-cell communication. This phenomenon, which relies on the interac tion of a diffusible signal molecule (e.g. an N-acylhomoserine lactone) wit h a sensor or transcriptional activator to couple gene expression with cell population density, has become known as 'quorum sensing'. Although the siz e of the 'quorum' is likely to be highly variable and influenced by the dif fusibility of the signal molecule within infected tissues, nevertheless quo rum-sensing signal molecules can be detected in vivo in both experimental a nimal model and human infections. Furthermore, certain quorum-sensing molec ules have been shown to possess pharmacological and immunomodulatory activi ty such that they may function as virulence determinants per se. As a conse quence, quorum sensing constitutes a novel therapeutic target for the desig n of small molecular antagonists capable of attenuating virulence through t he blockade of bacterial cell-cell communication.