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Toxins (Basel). 2017 Jan 13;9(1). pii: E34. doi: 10.3390/toxins9010034.

Distinct Neurotoxicity Profile of Listeriolysin O from Listeria monocytogenes.

Author information

1
DFG Membrane/Cytoskeleton Interaction Group, Institute of Pharmacology and Toxicology & Rudolf Virchow Center for Experimental Biomedical Science, University of Würzburg, Versbacherstr. 9, 97078 Würzburg, Germany. jana_maurer@t-online.de.
2
Institute of Physiology and Pathophysiology, Heidelberg University, Im Neuenheimer Feld 326, 69120 Heidelberg, Germany. jana_maurer@t-online.de.
3
DFG Membrane/Cytoskeleton Interaction Group, Institute of Pharmacology and Toxicology & Rudolf Virchow Center for Experimental Biomedical Science, University of Würzburg, Versbacherstr. 9, 97078 Würzburg, Germany. sabrina.hupp@ana.unibe.ch.
4
Institute of Anatomy, University of Bern, Baltzerstrasse 2, 3012 Bern, Switzerland. sabrina.hupp@ana.unibe.ch.
5
DFG Membrane/Cytoskeleton Interaction Group, Institute of Pharmacology and Toxicology & Rudolf Virchow Center for Experimental Biomedical Science, University of Würzburg, Versbacherstr. 9, 97078 Würzburg, Germany. carolin_bischoff@gmx.de.
6
DFG Membrane/Cytoskeleton Interaction Group, Institute of Pharmacology and Toxicology & Rudolf Virchow Center for Experimental Biomedical Science, University of Würzburg, Versbacherstr. 9, 97078 Würzburg, Germany. christina.foertsch@pharmalex.com.
7
Chair of Microbial Infection and Immunity, Institute of Microbiology and Infection, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. t.j.mitchell@bham.ac.uk.
8
Institute for Medical Microbiology, University of Giessen, Schubertstr. 81, 35392 Giessen, Germany. trinad.chakraborty@mikrobio.med.uni-giessen.de.
9
DFG Membrane/Cytoskeleton Interaction Group, Institute of Pharmacology and Toxicology & Rudolf Virchow Center for Experimental Biomedical Science, University of Würzburg, Versbacherstr. 9, 97078 Würzburg, Germany. asparouh.iliev@ana.unibe.ch.
10
Institute of Anatomy, University of Bern, Baltzerstrasse 2, 3012 Bern, Switzerland. asparouh.iliev@ana.unibe.ch.

Abstract

Cholesterol-dependent cytolysins (CDCs) are protein toxins that originate from Gram-positive bacteria and contribute substantially to their pathogenicity. CDCs bind membrane cholesterol and build prepores and lytic pores. Some effects of the toxins are observed in non-lytic concentrations. Two pathogens, Streptococcus pneumoniae and Listeria monocytogenes, cause fatal bacterial meningitis, and both produce toxins of the CDC family-pneumolysin and listeriolysin O, respectively. It has been demonstrated that pneumolysin produces dendritic varicosities (dendrite swellings) and dendritic spine collapse in the mouse neocortex, followed by synaptic loss and astrocyte cell shape remodeling without elevated cell death. We utilized primary glial cultures and acute mouse brain slices to examine the neuropathological effects of listeriolysin O and to compare it to pneumolysin with identical hemolytic activity. In cultures, listeriolysin O permeabilized cells slower than pneumolysin did but still initiated non-lytic astrocytic cell shape changes, just as pneumolysin did. In an acute brain slice culture system, listeriolysin O produced dendritic varicosities in an NMDA-dependent manner but failed to cause dendritic spine collapse and cortical astrocyte reorganization. Thus, listeriolysin O demonstrated slower cell permeabilization and milder glial cell remodeling ability than did pneumolysin and lacked dendritic spine collapse capacity but exhibited equivalent dendritic pathology.

KEYWORDS:

acute slices; dendritic spines; listeriolysin O; meningitis; varicosities

PMID:
28098781
PMCID:
PMC5308266
DOI:
10.3390/toxins9010034
[Indexed for MEDLINE]
Free PMC Article

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