TY - JOUR TI - Perforin-2 is essential for intracellular defense of parenchymal cells and phagocytes against pathogenic bacteria AU - McCormack, Ryan M AU - de Armas, Lesley R AU - Shiratsuchi, Motoaki AU - Fiorentino, Desiree G AU - Olsson, Melissa L AU - Lichtenheld, Mathias G AU - Morales, Alejo AU - Lyapichev, Kirill AU - Gonzalez, Louis E AU - Strbo, Natasa AU - Sukumar, Neelima AU - Stojadinovic, Olivera AU - Plano, Gregory V AU - Munson, George P AU - Tomic-Canic, Marjana AU - Kirsner, Robert S AU - Russell, David G AU - Podack, Eckhard R A2 - Cossart, Pascale VL - 4 PY - 2015 DA - 2015/09/24 SP - e06508 C1 - eLife 2015;4:e06508 DO - 10.7554/eLife.06508 UR - https://doi.org/10.7554/eLife.06508 AB - 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. KW - MRSA KW - ROS KW - NO KW - S. typhimurium KW - Mycobacterium tuberculosis KW - pathogenic bacteria JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -