Regulation of Competence Development in Haemophilus influenzae: Proposed Competence Regulatory Elements are CRP-Binding Sites

Development of competence for DNA uptake by the bacterium Haemophilus influenzae is tightly regulated, and expression of the cellʹs complement of competence genes is absolutely dependent on the cAMP–CRP complex. A second regulator of competence may maximize competence under starvation conditions. Several investigators have recently identified a consensus sequence (competence regulatory element, CRE) in the promoter regions of some competence genes and have proposed that this may be a binding site for Sxy (TfoX), a putative positive regulator of competence. However, a scoring method that reliably ranks candidate binding sites according to affinity for the cognate binding protein predicts that the cAMP–CRP complex will bind CRE sequences with high affinity. Moreover, the predicted Sxy protein lacks recognizable DNA-binding motifs and has not been shown to bind DNA. No other consensus sequences (putative binding sites) were identified in the promoter regions of competence genes. These observations suggest that the proposed competence-specific regulatory elements are in fact CRP-binding sites, and highlight the central role of cAMP—an established bacterial mediator of the response to nutritional stress—in competence regulation. Minor sequence elements uniquely conserved in the set of CRE sequences are predicted to reduce CRP affinity, and a model is suggested in which a secondary regulator of competence genes may interact with CRP under certain conditions to stabilize the initiation complex.