title: Microvesicle shedding and lysosomal repair fulfill divergent cellular needs during the repair of streptolysin O-induced plasmalemmal damage.
abstract: Pathogenic bacteria secrete pore-forming toxins that permeabilize the plasma membrane of host cells. Nucleated cells possess protective mechanisms that repair toxin-damaged plasmalemma. Currently two putative repair scenarios are debated: either the isolation of the damaged membrane regions and their subsequent expulsion as microvesicles (shedding) or lysosome-dependent repair might allow the cell to rid itself of its toxic cargo and prevent lysis. Here we provide evidence that both mechanisms operate in tandem but fulfill diverse cellular needs. The prevalence of the repair strategy varies between cell types and is guided by the severity and the localization of the initial toxin-induced damage, by the morphology of a cell and, most important, by the incidence of the secondary mechanical damage. The surgically precise action of microvesicle shedding is best suited for the instant elimination of individual toxin pores, whereas lysosomal repair is indispensable for mending of self-inflicted mechanical injuries following initial plasmalemmal permeabilization by bacterial toxins. Our study provides new insights into the functioning of non-immune cellular defenses against bacterial pathogens.
authors.affiliation: Department of Cell Biology, Institute of Anatomy, University of Bern, Bern, Switzerland.
authors.forename: Alexander P
authors.initials: AP
authors.lastname: Atanassoff
authors.affiliation: Department of Cell Biology, Institute of Anatomy, University of Bern, Bern, Switzerland.
authors.forename: Heidi
authors.initials: H
authors.lastname: Wolfmeier
authors.affiliation: Department of Cell Biology, Institute of Anatomy, University of Bern, Bern, Switzerland.
authors.forename: Roman
authors.initials: R
authors.lastname: Schoenauer
authors.affiliation: Department of Cell Biology, Institute of Anatomy, University of Bern, Bern, Switzerland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Hostettler
authors.affiliation: Department of Protection, Norwegian Defence Research Establishment, Kjeller, Norway.
authors.forename: Avi
authors.initials: A
authors.lastname: Ring
authors.affiliation: Department of Cell Biology, Institute of Anatomy, University of Bern, Bern, Switzerland.
authors.forename: Annette
authors.initials: A
authors.lastname: Draeger
authors.affiliation: Department of Cell Biology, Institute of Anatomy, University of Bern, Bern, Switzerland.
authors.forename: Eduard B
authors.initials: EB
authors.lastname: Babiychuk
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D001426:Bacterial Proteins / Q000494:pharmacology; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival; D055252:Cell-Derived Microparticles / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D007113:Immunity, Innate; D008247:Lysosomes / Q000502:physiology*; D008561:Membrane Fusion; D009218:Myosins / Q000378:metabolism; D013301:Streptolysins / Q000494:pharmacology*
chemical_list: D001426:Bacterial Proteins; D013301:Streptolysins; C025964:streptolysin O; D009218:Myosins