title: Perforin-2 is essential for intracellular defense of parenchymal cells and phagocytes against pathogenic bacteria.
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.
authors.affiliation: Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, United States.
authors.forename: Ryan M
authors.initials: RM
authors.lastname: McCormack
authors.affiliation: Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, United States.
authors.forename: Lesley R
authors.initials: LR
authors.lastname: de Armas
authors.affiliation: Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, United States.
authors.forename: Motoaki
authors.initials: M
authors.lastname: Shiratsuchi
authors.affiliation: Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, United States.
authors.forename: Desiree G
authors.initials: DG
authors.lastname: Fiorentino
authors.affiliation: Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, United States.
authors.forename: Melissa L
authors.initials: ML
authors.lastname: Olsson
authors.affiliation: Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, United States.
authors.forename: Mathias G
authors.initials: MG
authors.lastname: Lichtenheld
authors.affiliation: Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, United States.
authors.forename: Alejo
authors.initials: A
authors.lastname: Morales
authors.affiliation: Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, United States.
authors.forename: Kirill
authors.initials: K
authors.lastname: Lyapichev
authors.affiliation: Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, United States.
authors.forename: Louis E
authors.initials: LE
authors.lastname: Gonzalez
authors.affiliation: Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, United States.
authors.forename: Natasa
authors.initials: N
authors.lastname: Strbo
authors.affiliation: Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, United States.
authors.forename: Neelima
authors.initials: N
authors.lastname: Sukumar
authors.affiliation: Wound Healing and Regenerative Medicine Research Program, Department of Dermatology and Cutaneous Surgery, Miller School of Medicine, University of Miami, Miami, United States.
authors.forename: Olivera
authors.initials: O
authors.lastname: Stojadinovic
authors.affiliation: Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, United States.
authors.forename: Gregory V
authors.initials: GV
authors.lastname: Plano
authors.affiliation: Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, United States.
authors.forename: George P
authors.identifier: http://orcid.org/0000-0002-3692-8199
authors.initials: GP
authors.lastname: Munson
authors.affiliation: Wound Healing and Regenerative Medicine Research Program, Department of Dermatology and Cutaneous Surgery, Miller School of Medicine, University of Miami, Miami, United States.
authors.forename: Marjana
authors.initials: M
authors.lastname: Tomic-Canic
authors.affiliation: Wound Healing and Regenerative Medicine Research Program, Department of Dermatology and Cutaneous Surgery, Miller School of Medicine, University of Miami, Miami, United States.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Kirsner
authors.affiliation: Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, United States.
authors.forename: David G
authors.initials: DG
authors.lastname: Russell
authors.affiliation: Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, United States.
authors.forename: Eckhard R
authors.initials: ER
authors.lastname: Podack
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D007113:Immunity, Innate; D018345:Mice, Knockout; D050296:Microbial Viability; D010586:Phagocytes; D052899:Pore Forming Cytotoxic Proteins / Q000378:metabolism*; D012481:Salmonella Infections, Animal / Q000276:immunology*; D012486:Salmonella typhimurium / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D013203:Staphylococcal Infections / Q000276:immunology*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D016019:Survival Analysis; D014617:Vacuoles / Q000382:microbiology
chemical_list: D052899:Pore Forming Cytotoxic Proteins; C510469:perforin 2
keywords: E. coli; MRSA; Mycobacterium tuberculosis; NO; ROS; S. typhimurium; human; immunology; infectious disease; microbiology; mouse; pathogenic bacteria