title: Type IV pilus protein PilA of Pseudomonas aeruginosa modulates calcium signaling through binding the calcium-modulating cyclophilin ligand.
abstract: The lungs are a major site of Pseudomonas aeruginosa infection in patients with compromised immune systems. We have shown that a large number of cells of the P. aeruginosa wild-type PAO1 strain invade cultured human bronchial epithelial cells (BEAS-2B). In the present study, we investigated whether P. aeruginosa pilus protein PilA might modulate cellular functions by binding to unknown factor(s) in human host cells. Using a yeast two-hybrid screen, we showed that the calcium-modulating cyclophilin ligand (CAMLG), which is involved in Ca(2+) signaling, was the major host cell PilA binding protein. Overexpression of the pilA gene in BEAS-2B cells resulted in a significant increase in cytoplasmic Ca(2+) and consequent upregulation of the activity of the nuclear factor of activated T cells, followed by induction of cyclooxygenase 2 gene expression. Infection of BEAS-2B cells with the P. aeruginosa wild-type strain, but not with the pilA gene knockout strain (ΔpilA), caused a significant increase in intracellular Ca(2+) concentration in infected cells. Therefore, we propose a novel bacterial strategy for PilA modulation of intracellular Ca(2+) signaling through intracellular PilA-CAMLG interaction.
authors.affiliation: Department of Microbiology and Infection Control Sciences, Kyoto Pharmaceutical University, Yamashina, Kyoto, 607-8414, Japan. okuda@chs.pref.kagawa.jp
authors.forename: Jun
authors.initials: J
authors.lastname: Okuda
authors.forename: Naoki
authors.initials: N
authors.lastname: Hayashi
authors.forename: Munenori
authors.initials: M
authors.lastname: Arakawa
authors.forename: Shu
authors.initials: S
authors.lastname: Minagawa
authors.forename: Naomasa
authors.initials: N
authors.lastname: Gotoh
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D018938:Caco-2 Cells; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism; D036781:Fimbriae Proteins / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D054884:Host-Pathogen Interactions; D006801:Humans; D018613:Microscopy, Confocal; D011485:Protein Binding; D011552:Pseudomonas Infections; D011550:Pseudomonas aeruginosa / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C089404:CAMLG protein, human; D036781:Fimbriae Proteins; D002118:Calcium