Cell signaling by the type IV pili of pathogenic Nisseria

Neisseria gonorrhoeae and Neisseria meningitidis are Gram-negative bacterial pathogens that infect human mucosal epithelia. Type TV pilus-mediated adherence of these bacteria is a crucial early event for establishment of infection. In this work, we show that the type IV pill transduce a signal into the eucaryotic host cell. Purified adherent pill, but not pill from a low binding mutant, trigger an increase in the cytosolic free calcium ([Ca2+](i)) in target epithelial cells, a signal known to control many cellular responses. The [Ca2+](i) increase was blocked by antibodies against CD46, a putative pilus receptor, suggesting a role for this protein in signal transduction. Pilus-mediated attachment was inhibited by depletion of host cell intracellular Ca2+ stores but not by removal of extracellular Ca2+. Further, kinase inhibition studies showed that pilus-mediated adherence is dependent on casein kinase II. In summary, these data reveal a novel function of the type IV pill, namely induction of signal transduction pathways in host cells.