Journalartikel
Autorenliste: La Pietra, Luigi; Hudel, Martina; Pillich, Helena; Abu Mraheil, Mobarak; Berisha, Besim; Aden, Sasa; Hodnik, Vesna; Lochnit, Gunter; Rafiq, Amir; Perniss, Alexander; Anderluh, Gregor; Chakraborty, Trinad
Jahr der Veröffentlichung: 2020
Seiten: 1505-1516
Zeitschrift: The Journal of Infectious Diseases
Bandnummer: 222
Heftnummer: 9
ISSN: 0022-1899
eISSN: 1537-6613
DOI Link: https://doi.org/10.1093/infdis/jiaa022
Verlag: Oxford University Press
Background. Bacterial toxins disrupt plasma membrane integrity with multitudinous effects on host cells. The secreted poreforming 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. Methods. Combining 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. Results. Here, 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. Conclusions. Our 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.
Abstract:
Zitierstile
Harvard-Zitierstil: La Pietra, L., Hudel, M., Pillich, H., Abu Mraheil, M., Berisha, B., Aden, S., et al. (2020) Phosphocholine Antagonizes Listeriolysin O-Induced Host Cell Responses of Listeria monocytogenes, The Journal of Infectious Diseases, 222(9), pp. 1505-1516. https://doi.org/10.1093/infdis/jiaa022
APA-Zitierstil: La Pietra, L., Hudel, M., Pillich, H., Abu Mraheil, M., Berisha, B., Aden, S., Hodnik, V., Lochnit, G., Rafiq, A., Perniss, A., Anderluh, G., & Chakraborty, T. (2020). Phosphocholine Antagonizes Listeriolysin O-Induced Host Cell Responses of Listeria monocytogenes. The Journal of Infectious Diseases. 222(9), 1505-1516. https://doi.org/10.1093/infdis/jiaa022
Schlagwörter
HEMOLYSIN; INTRACELLULAR GENE-EXPRESSION; listeriolysin O; PC-PLC; phosphocholine; PHOSPHOLIPASE-C ACTIVITY; pore-forming toxin; ZINC METALLOPROTEASE
