Abstract:
:Perforin-2 (MPEG1) is a pore-forming, antibacterial protein with broad-spectrum activity. Perforin-2 is expressed constitutively in phagocytes and inducibly in parenchymal, tissue-forming cells. In vitro, Perforin-2 prevents the intracellular replication and proliferation of bacterial pathogens in these cells. Perforin-2 knockout mice are unable to control the systemic dissemination of methicillin-resistant Staphylococcus aureus (MRSA) or Salmonella typhimurium and perish shortly after epicutaneous or orogastric infection respectively. In contrast, Perforin-2-sufficient littermates clear the infection. Perforin-2 is a transmembrane protein of cytosolic vesicles -derived from multiple organelles- that translocate to and fuse with bacterium containing vesicles. Subsequently, Perforin-2 polymerizes and forms large clusters of 100 Å pores in the bacterial surface with Perforin-2 cleavage products present in bacteria. Perforin-2 is also required for the bactericidal activity of reactive oxygen and nitrogen species and hydrolytic enzymes. Perforin-2 constitutes a novel and apparently essential bactericidal effector molecule of the innate immune system.
journal_name
Elifejournal_title
eLifeauthors
McCormack RM,de Armas LR,Shiratsuchi M,Fiorentino DG,Olsson ML,Lichtenheld MG,Morales A,Lyapichev K,Gonzalez LE,Strbo N,Sukumar N,Stojadinovic O,Plano GV,Munson GP,Tomic-Canic M,Kirsner RS,Russell DG,Podack ERdoi
10.7554/eLife.06508subject
Has Abstractpub_date
2015-09-24 00:00:00issn
2050-084Xjournal_volume
4pub_type
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