AI-2 quorum-sensing circuit in A. actinomycetemcomitans. For A. actinomycetemcomitans, we hypothesize that AI-2-dependent biofilm formation and other potential AI-2-mediated cellular processes may result from one or two possible pathways. AI-2 is initially bound by its periplasmic receptors and imported into the cell by ABC-type transporters associated with the lsr and rbs operons. Once inside the cell, AI-2 is presumed to be phosphorylated by LsrK, and phosphorylated AI-2 is thought to interact directly with LsrR, resulting in derepression of the lsr operon. However, LsrR may also interact with unphosphorylated AI-2, as suggested by Li et al. (21). Regulation of the QseBC two-component system may occur through direct interaction with AI-2, or its expression may be induced by LsrR. The QseBC two-component system in turn alters the expression of genes that mediate biofilm formation, and potentially other genes, including those important for iron acquisition.