In Streptococcus pneumoniae, the induction of genetic competence (and potentially virulence) is regulated by a CSP–mediated quorum-sensing system (5, 9). Quorum sensing involves the expression of early gene products encoded by two genetic loci, comAB and comCDE. Genes in the operon, comAB, encode an ATP-binding cassette transporter (ComA) and an accessory protein to ComA (ComB). These secretory proteins are involved in the processing and export of the CSP. The loci, comCDE, respectively encode the precursor to the CSP, a histidine kinase that acts as a CSP receptor, and a response regulator that activates both comAB and comCDE operons. A second two-component regulatory system, CiaH-CiaR, affects the development of competence by negatively regulating comCDE expression. Quorum-sensing signals initiate competence through activity of ComX, a global transcription modulator, which was shown to act as an alternate sigma factor (40). This sigma factor initiates the transcription of competence-specific operons involved in DNA uptake and recombination by recognizing a com-box (also referred to as cin-box) consensus sequence (TACGAATA) in their promoter regions (9, 41, 42). Several of these late competence-specific operons include cilA (ssb2), cilB (dal, like dprA in Haemophilus influenzae), cilC (like comC in Bacillus subtilis), cilD (or cglABCDE), cilE (or celAB), coi, cinA-recA, cfl (like comF in B. subtilis), and dpnA of the DpnII restriction system. pol, polymerase; P, phosphate.