title: Listeriolysin of Listeria monocytogenes forms Ca2+-permeable pores leading to intracellular Ca2+ oscillations.
abstract: Listeriolysin (LLO) is a major virulence factor of Listeria monocytogenes, a Gram-positive bacterium that can cause life-threatening diseases. Various signalling events and cellular effects, including modulation of gene expression, are triggered by LLO through unknown mechanisms. Here, we demonstrate that LLO applied extracellularly at sublytic concentrations causes long-lasting oscillations of the intracellular Ca2+ level of human embryonic kidney cells; resulting from a pulsed influx of extracellular Ca2+ through pores that are formed by LLO in the plasma membrane. Calcium influx does not require the activity of endogenous Ca2+ channels. LLO-formed pores are transient and oscillate between open and closed states. Pore formation and Ca2+ oscillations were also observed after exposure of cells to native Listeria monocytogenes. Our data identify LLO as a tool used by Listeria monocytogenes to manipulate the intracellular Ca2+ level without direct contact of the bacterium with the target cell. As Ca2+ oscillations modulate cellular signalling and gene expression, our findings provide a potential molecular basis for the broad spectrum of Ca2+-dependent cellular responses induced by LLO during Listeria infection.
authors.affiliation: Rudolf-Buchheim-Institute of Pharmacology, Justus-Liebig-University of Giessen, Frankfurter Str. 107, 35392 Giessen, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Repp
authors.forename: Zübeyde
authors.initials: Z
authors.lastname: Pamukçi
authors.forename: Andreas
authors.initials: A
authors.lastname: Koschinski
authors.forename: Eugen
authors.initials: E
authors.lastname: Domann
authors.forename: Ayub
authors.initials: A
authors.lastname: Darji
authors.forename: Jan
authors.initials: J
authors.lastname: Birringer
authors.forename: Dierk
authors.initials: D
authors.lastname: Brockmeier
authors.forename: Trinad
authors.initials: T
authors.lastname: Chakraborty
authors.forename: Florian
authors.initials: F
authors.lastname: Dreyer
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism; D001427:Bacterial Toxins; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D002460:Cell Line; D003603:Cytotoxins / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006460:Hemolysin Proteins; D006801:Humans; D007473:Ion Channels / Q000378:metabolism*; D008089:Listeria monocytogenes / Q000378:metabolism*; D018408:Patch-Clamp Techniques
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D003603:Cytotoxins; D005456:Fluorescent Dyes; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D007473:Ion Channels; C038705:hlyA protein, Listeria monocytogenes; D002118:Calcium