Multifaceted Activity of Listeriolysin O, the Cholesterol-Dependent Cytolysin of Listeria monocytogenes

  • Stephanie SeveauEmail author
Part of the Subcellular Biochemistry book series (SCBI, volume 80)


The cholesterol-dependent cytolysins (CDCs) are a large family of pore-forming toxins that are produced by numerous Gram-positive bacterial pathogens. These toxins are released in the extracellular environment as water-soluble monomers or dimers that bind to cholesterol-rich membranes and assemble into large pore complexes. Depending upon their concentration, the nature of the host cell and membrane (cytoplasmic or intracellular) they target, the CDCs can elicit many different cellular responses. Among the CDCs, listeriolysin O (LLO), which is a major virulence factor of the facultative intracellular pathogen Listeria monocytogenes, is involved in several stages of the intracellular lifecycle of the bacterium and displays unique characteristics. It has long been known that following L. monocytogenes internalization into host cells, LLO disrupts the internalization vacuole, enabling the bacterium to replicate into the host cell cytosol. LLO is then used by cytosolic bacteria to spread from cell to cell, avoiding bacterial exposure to the extracellular environment. Although LLO is continuously produced during the intracellular lifecycle of L. monocytogenes, several processes limit its toxicity to ensure the survival of infected cells. It was previously thought that LLO activity was limited to mediating vacuolar escape during bacterial entry and cell to cell spreading. This concept has been challenged by compelling evidence suggesting that LLO secreted by extracellular L. monocytogenes perforates the host cell plasma membrane, triggering important host cell responses. This chapter provides an overview of the well-established intracellular activity of LLO and the multiple roles attributed to LLO secreted by extracellular L. monocytogenes.


Bacterial toxin Cholesterol-dependent cytolysin Infectious disease Listeria monocytogenes Listeriolysin O 



Anthrolysin O


Acid sphingomyelinase


Cholesterol-dependent cytolysin


Cystic fibrosis transmembrane conductance regulator


Endoplasmic reticulum


Extracellular-signal-regulated kinase


Gamma-interferon inducible lysosomal thiol reductase


Hepatocyte growth factor receptor


Human neutrophil peptide


Intermedilysin O


Internalin A


Internalin B


Isopropyl β-D-1-thiogalactopyranoside


C-Jun N-terminal kinase


Listeria pathogenicity island


Listeriolysin O


Mitogen-activated protein kinase


Major histocompatibility complex




NOD-like receptors


Double-stranded RNA activated protein kinase (PKR)-like ER kinase


Phosphatidylcholine-specific phospholipase


Phosphatidylinositol-specific phospholipase


Perfringolysin O




Positive regulatory factor A


Reactive oxygen species


Streptolysin O


Small ubiquitin-like modifier


Unfolded protein response


Untranslated region



This work was made possible by Grant R01AI107250 (Stephanie Seveau) from the National Institutes of Health (NIAID) and its contents are solely the responsibility of the author and do not necessarily represent the official views of the NIAID.


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© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  1. 1.Department of Microbiology, Department of Microbial Infection and ImmunityThe Ohio State UniversityColumbusUSA

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