title: Distinct Neurotoxicity Profile of Listeriolysin O from Listeria monocytogenes.
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 pneumoniaeandListeria 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.
authors.affiliation: 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.|Institute of Physiology and Pathophysiology, Heidelberg University, Im Neuenheimer Feld 326, 69120 Heidelberg, Germany. jana_maurer@t-online.de.
authors.forename: Jana
authors.initials: J
authors.lastname: Maurer
authors.affiliation: 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.|Institute of Anatomy, University of Bern, Baltzerstrasse 2, 3012 Bern, Switzerland. sabrina.hupp@ana.unibe.ch.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Hupp
authors.affiliation: 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.
authors.forename: Carolin
authors.initials: C
authors.lastname: Bischoff
authors.affiliation: 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.
authors.forename: Christina
authors.initials: C
authors.lastname: Foertsch
authors.affiliation: 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.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Mitchell
authors.affiliation: Institute for Medical Microbiology, University of Giessen, Schubertstr. 81, 35392 Giessen, Germany. trinad.chakraborty@mikrobio.med.uni-giessen.de.
authors.forename: Trinad
authors.initials: T
authors.lastname: Chakraborty
authors.affiliation: 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.|Institute of Anatomy, University of Bern, Baltzerstrasse 2, 3012 Bern, Switzerland. asparouh.iliev@ana.unibe.ch.
authors.forename: Asparouh I
authors.initials: AI
authors.lastname: Iliev
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects* / Q000473:pathology; D001426:Bacterial Proteins / Q000235:genetics / Q000633:toxicity; D001427:Bacterial Toxins / Q000235:genetics / Q000633:toxicity*; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D002463:Cell Membrane Permeability / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D049229:Dendritic Spines / Q000187:drug effects* / Q000473:pathology; D006360:Heat-Shock Proteins / Q000235:genetics / Q000633:toxicity*; D006460:Hemolysin Proteins / Q000235:genetics / Q000633:toxicity*; D008089:Listeria monocytogenes / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D009498:Neurotoxins / Q000235:genetics / Q000633:toxicity*; D061251:Primary Cell Culture; D011994:Recombinant Proteins; D013301:Streptolysins / Q000235:genetics / Q000633:toxicity
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D009498:Neurotoxins; D011994:Recombinant Proteins; D013301:Streptolysins; C032290:plY protein, Streptococcus pneumoniae; C038705:hlyA protein, Listeria monocytogenes
keywords: acute slices; dendritic spines; listeriolysin O; meningitis; varicosities