Open AccessThe multiple mechanisms of Ca 2+ signalling by listeriolysin O, the cholesterol‐dependent cytolysin of Listeria monocytogenes
Author(s) -
Gekara Nelson O.,
Westphal Kathrin,
Ma Bin,
Rohde Manfred,
Groebe Lothar,
Weiss Siegfried
Publication year - 2007
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/j.1462-5822.2007.00932.x
Subject(s) - listeriolysin o , biology , intracellular , listeria monocytogenes , microbiology and biotechnology , cytolysin , extracellular , intracellular parasite , endoplasmic reticulum , biochemistry , listeria , bacteria , virulence , genetics , gene
Summary Cholesterol‐dependent cytolysins (CDCs) represent a large family of conserved pore‐forming toxins produced by several Gram‐positive bacteria such as Listeria monocytogenes, Streptococcus pyrogenes and Bacillus anthracis . These toxins trigger a broad range of cellular responses that greatly influence pathogenesis. Using mast cells, we demonstrate that listeriolysin O (LLO), a prototype of CDCs produced by L. monocytogenes , triggers cellular responses such as degranulation and cytokine synthesis in a Ca 2+ ‐dependent manner. Ca 2+ signalling by LLO is due to Ca 2+ influx from extracellular milieu and release of from intracellular stores. We show that LLO‐induced release of Ca 2+ from intracellular stores occurs via at least two mechanisms: (i) activation of intracellular Ca 2+ channels and (ii) a Ca 2+ channels independent mechanism. The former involves PLC‐IP 3 R operated Ca 2+ channels activated via G‐proteins and protein tyrosine kinases. For the latter, we propose a novel mechanism of intracellular Ca 2+ release involving injury of intracellular Ca 2+ stores such as the endoplasmic reticulum. In addition to Ca 2+ signalling, the discovery that LLO causes damage to an intracellular organelle provides a new perspective in our understanding of how CDCs affect target cells during infection by the respective bacterial pathogens.