Intimate adhesion of Neisseria meningitidis to human epithelial cells is under the control of the crgA gene, a novel LysR-type transcriptional regulator

PilC1, a pilus-associated protein in Neisseria meningitidis, is a key eleme nt in initial meningococcal adhesion to target cells, A promoter element (C REN, contact regulatory element of Neisseria) is responsible for the transi ent induction of this gene upon cell contact. crgA (contact-regulated gene A) encodes a transcriptional regulator whose expression is also induced upo n cell contact from a promoter region similar to the CREN of pilC1, CrgA sh ows significant sequence homologies to LysR-type transcriptional regulators . Its inactivation in meningococci provokes a dramatic reduction in bacteri al adhesion to epithelial cells. Moreover, this mutant is unable to undergo intimate adhesion to epithelial cells or to provoke effacing of microvilli on infected cells. Purified CrgA is able to bind to pilC1 and crgA promote rs, and CrgA seems to repress the expression of pilC1 and crgA. Our results support a dynamic model of bacteria-cell interaction involving a network o f regulators acting in cascade. CrgA could be an intermediate regulator in such a network.