CONVERGENT SENSING PATHWAYS MEDIATE RESPONSE TO 2 EXTRACELLULAR COMPETENCE FACTORS IN BACILLUS-SUBTILIS

Development of genetic competence in Bacillus subtilis is regulated by extracellular signaling molecules, including the ComX pheromone, a modified 9- or 10-amino-acid peptide. Here, we present characterization of a second extracellular competence stimulating factor (CSF). CSF appears to be, at least in part, a small peptide of between 520 and 720 daltons. Production of CSF requires several genes that are needed both for initiation of sporulation and development of competence (spoOH, spoOA, spoOB, and spoOF). Although both peptide factors regulate competence, two different sensing pathways mediate the response to the ComX pheromone and CSF. Analysis of double mutants indicated that ComX pheromone is on the same genetic pathway as the membrane-bound histidine protein kinase encoded by comP and that CSF is on the same genetic pathway as the oligopeptide permease encoded by spoOK. Furthermore, the cellular response to partly purified ComX pheromone requires the ComP histidine protein kinase, whereas the response to partly purified CSF requires the SpoOK oligopeptide permease. These two sensing pathways converge to activate transcription of comS (in the srfA operon), a key regulatory factor required for activation of additional competence genes. Both factors and their convergent sensing pathways are required for normal development of competence and might function to integrate different physiological signals.