title: ExoU is a potent intracellular phospholipase.
abstract: The combination of a large genome encoding metabolic versatility and conserved secreted virulence determinants makes Pseudomonas aeruginosa a model pathogen that can be used to study host-parasite interactions in many eukaryotic hosts. One of the virulence regulons that likely plays a role in the ability of P. aeruginosa to avoid innate immune clearance in mammals is a type III secretion system (TTSS). Upon cellular contact, the P. aeruginosa TTSS is capable of delivering a combination of at least four different effector proteins, exoenzyme S (ExoS), ExoT, ExoU, and ExoY. Two of the four translocated proteins, ExoS and ExoU, are cytotoxic to cells during infection and transfection. The mechanism of cytotoxicity of ExoS is unclear. ExoU, however, has recently been characterized as a member of the phospholipase A family of enzymes, possessing at least phospholipase A2 activity. Similar to ExoS, ExoT and ExoY, ExoU requires either a eukaryotic-specific modification or cofactor for its activity in vitro. The biologic effects of minimal expression of ExoU in yeast can be visualized by membrane damage to different organelles and fragmentation of the vacuole. In mammalian cells, the direct injection of ExoU causes irreversible damage to cellular membranes and rapid necrotic death. ExoU likely represents a unique enzyme and is the first identified phopholipase virulence factor that is translocated into the cytosol by TTSS.
authors.affiliation: Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, Wisconsin 53226, USA.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Sato
authors.forename: Dara W
authors.initials: DW
authors.lastname: Frank
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001427:Bacterial Toxins / Q000378:metabolism*; D002265:Carboxylic Ester Hydrolases / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D044404:Genomic Islands; D008969:Molecular Sequence Data; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D010940:Plant Proteins / Q000235:genetics / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity; D018805:Sepsis / Q000276:immunology / Q000382:microbiology; D016415:Sequence Alignment; D013379:Substrate Specificity; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D037521:Virulence Factors / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004268:DNA-Binding Proteins; C095092:ExsA protein, bacteria; D010940:Plant Proteins; D015534:Trans-Activators; D037521:Virulence Factors; C043222:patatin protein, Solanum tuberosum; C111749:pseudomonas exoprotein A protein, Pseudomonas aeruginosa; D002265:Carboxylic Ester Hydrolases; D010741:Phospholipases A; D054467:Phospholipases A2