Cell signaling by the type IV pili of pathogenic Neisseria.
Neisseria gonorrhoeae and Neisseria meningitidis are Gram-negative bacterial pathogens that infect human mucosal epithelia. Type IV pilus-mediated adherence of these bacteria is a crucial early event for establishment of infection. In this work, we show that the type IV pili transduce a signal into the eucaryotic host cell. Purified adherent pili, but not pili 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 pili, namely induction of signal transduction pathways in host cells.
Källström
H
H
Microbiology and Tumorbiology Center, Karolinska Institute, S-171 77, Stockholm, Sweden.
Islam
M S
MS
Berggren
P O
PO
Jonsson
A B
AB
D015703:Antigens, CD / Q000276:immunology; D001422:Bacterial Adhesion; D002118:Calcium / Q000378:metabolism; D047390:Casein Kinase II; D002450:Cell Communication; D003600:Cytosol / Q000378:metabolism; D010861:Fimbriae, Bacterial / Q000502:physiology*; D006801:Humans; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000276:immunology; D009344:Neisseria gonorrhoeae / Q000166:cytology*; D009345:Neisseria meningitidis / Q000166:cytology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; C497857:CD46 protein, human; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases; D002118:Calcium