Specificity and genetic polymorphism of the Bacillus competence quorum-sensing system

A quorum-sensing mechanism involving the pheromone ComX and the ComP-ComA t wo-component system controls natural competence in Bacillus subtilis. ComX is expressed as a cytoplasmic inactive precursor that is released into the extracellular medium as a cleaved, modified decapeptide. This process requi res the product of come. In the presence of ComX, the membrane-localized Co mP histidine kinase activates the response regulator ComA. We compared the sequences of the quorum-sensing genes from four closely related bacilli, an d we report extensive genetic polymorphism extending through come, comX, an d the 5' two-thirds of comP. This part of ComP encodes the membrane-localiz ed and linker domains of the sensor protein. We also determined the sequenc es of the comX genes of four additional wild-type bacilli and tested the in vivo activities of all eight pheromones on isogenic strains containing fou r different ComP receptor proteins. A striking pattern of specificity was d iscovered, providing strong evidence that the pheromone contacts ComP direc tly. Furthermore, we show that coexpression of come and comX in Escherichia coli leads to the production of active pheromone in the medium, demonstrat ing that come is the only dedicated protein required for the processing, mo dification, and release of arrive competence pheromone. Some of the implica tions of these findings for the evolution and the mechanism of the quorum-s ensing system are discussed.