CELL SIGNALING BY THE TYPE-IV PILI OF PATHOGENIC NISSERIA

Neisseria gonorrhoeae and Neisseria meningitidis are Gram-negative bac terial pathogens that infect human mucosal epithelia. Type TV pilus-me diated adherence of these bacteria is a crucial early event for establ ishment of infection. In this work, we show that the type IV pill tran sduce a signal into the eucaryotic host cell. Purified adherent pill, but not pill from a low binding mutant, trigger an increase in the cyt osolic free calcium ([Ca2+](i)) in target epithelial cells, a signal k nown to control many cellular responses. The [Ca2+](i) increase was bl ocked by antibodies against CD46, a putative pilus receptor, suggestin g a role for this protein in signal transduction. Pilus-mediated attac hment was inhibited by depletion of host cell intracellular Ca2+ store s but not by removal of extracellular Ca2+. Further, kinase inhibition studies showed that pilus-mediated adherence is dependent on casein k inase II. In summary, these data reveal a novel function of the type I V pill, namely induction of signal transduction pathways in host cells .