Fig. 6.
Model by which Epi and AI-3 could cross-talk to regulate expression of the type III secretion system and flagella and motility. Our data suggest that both AI-3 and Epi are recognized by the same receptor, which is probably in the outer membrane of the bacteria because of the nonpolar nature of both AI-3 and Epi. These signals might be imported to the periplasmic space where they interact with either one major sensor kinase that directs the transcription of other sensor kinases or with more than one sensor kinase. We favor the latter hypothesis, given our results that a qseC mutant, which does not respond to either AI-3 or Epi (Figs. 2 and 4), only affects the QS regulation of the flagella regulon and not the locus of enterocyte effacement (LEE) genes (6). The interaction of AI-3 and Epi with more than one sensor kinase would also give some "timing" to this system, which is a desirable feature, given that it would be inefficient for EHEC to produce both the LEE type III secretion system and flagella at the same time. Therefore, we hypothesize that EHEC activates expression of the flagella regulon first through QseBC and the LEE genes, and at a later time through another yet-unidentified sensor kinase.