Proteolytic Regulation of Competence Development in the Genus Streptococcus: Implications in Competence, Stress Response and Antibacterial Therapy

Abstract

Competence development for natural genetic transformation is widespread in bacteria, although it is a transient physiological state in which bacteria are capable of taking up and integrating exogenous DNA. Activation of competence enables the recipient bacteria to gain new genes, promoting the emergence of genetic variation, antibiotic resistance and evolution of virulence factors. It has been well studied that competence activation in bacteria requires one or more signal transduction pathways, many competence proteins and a complex regulatory network, which are finely controlled by a competence-specific master regulator. In the Genus Streptococcus, an alternative sigma factor, SigX coded by comX, is such a master regulator. The transcriptional activation of comX is the key step of competence induction in nearly all members of Streptococci. Although much is known of the regulatory cascade leading to competence induction, it was not until recently that a negative regulation of competence by a mechanism that involves regulated proteolysis of SigX has been recognized to play an important role in competence development in these bacteria. In particular, an adaptor protein MecA is found to target SigX for degradation by the proteases ClpC/ClpP, profoundly affecting the stability of SigX during competence development. Interestingly, SigX-mediated competence appears to be antagonistically connected with antibiotic-induced stress response by an unknown mechanism that involves activities of MecA and the Clp protease family. This discovery has added a new level of the complexity of competence regulatory network in Streptococci, leading to further investigation of such proteolytic regulation in competence, stress response, and antibacterial therapy.