Phosphocholine Antagonizes Listeriolysin O-Induced Host Cell Responses of Listeria monocytogenes
| Autor: | Besim Berisha, Günter Lochnit, Helena Pillich, Saša Aden, Alexander Perniss, Luigi La Pietra, Amir Rafiq, Gregor Anderluh, Mobarak Abu Mraheil, Martina Hudel, Trinad Chakraborty, Vesna Hodnik |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Phosphorylcholine Bacterial Toxins 030106 microbiology Apoptosis medicine.disease_cause Microbiology Hemolysin Proteins 03 medical and health sciences chemistry.chemical_compound Listeria monocytogenes Calcium flux medicine Extracellular Humans Immunology and Allergy Heat-Shock Proteins Phosphocholine Membrane Potential Mitochondrial Caspase 3 Chemistry Listeriolysin O Mitochondria Cytosol 030104 developmental biology Infectious Diseases Calcium Streptolysin Reactive Oxygen Species Intracellular HeLa Cells |
| Zdroj: | The Journal of Infectious Diseases. 222:1505-1516 |
| ISSN: | 1537-6613 0022-1899 |
| DOI: | 10.1093/infdis/jiaa022 |
| Popis: | BackgroundBacterial toxins disrupt plasma membrane integrity with multitudinous effects on host cells. The secreted pore-forming toxin listeriolysin O (LLO) of the intracellular pathogen Listeria monocytogenes promotes egress of the bacteria from vacuolar compartments into the host cytosol often without overt destruction of the infected cell. Intracellular LLO activity is tightly controlled by host factors including compartmental pH, redox, proteolytic, and proteostatic factors, and inhibited by cholesterol.MethodsCombining infection studies of L. monocytogenes wild type and isogenic mutants together with biochemical studies with purified phospholipases, we investigate the effect of their enzymatic activities on LLO.ResultsHere, we show that phosphocholine (ChoP), a reaction product of the phosphatidylcholine-specific phospholipase C (PC-PLC) of L. monocytogenes, is a potent inhibitor of intra- and extracellular LLO activities. Binding of ChoP to LLO is redox-independent and leads to the inhibition of LLO-dependent induction of calcium flux, mitochondrial damage, and apoptosis. ChoP also inhibits the hemolytic activities of the related cholesterol-dependent cytolysins (CDC), pneumolysin and streptolysin.ConclusionsOur study uncovers a strategy used by L. monocytogenes to modulate cytotoxic LLO activity through the enzymatic activity of its PC-PLC. This mechanism appears to be widespread and also used by other CDC pore-forming toxin-producing bacteria. |
| Databáze: | OpenAIRE |
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