Pseudolipasin A Is a Specific Inhibitor for Phospholipase A 2 Activity of Pseudomonas aeruginosa Cytotoxin ExoU
| Autor: | Xiaohua Li, Vincent T. Lee, Dara W. Frank, Stephen Lory, Stefan Pukatzki, Anastasia A. Kazimirova, Jin Huang, Jonathan P. Arm, Eriya Kikawada, Hiromi Sato |
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| Rok vydání: | 2007 |
| Předmět: |
Virulence Factors
Immunology Cell CHO Cells medicine.disease_cause Microbiology Phospholipases A Virulence factor Cricetulus Bacterial Proteins Cricetinae medicine Animals Secretion Enzyme Inhibitors Fluorenes biology Cytotoxins Pseudomonas aeruginosa Effector Molecular Pathogenesis Phospholipases A2 Infectious Diseases medicine.anatomical_structure Host cell cytoplasm biology.protein Exoenzyme lipids (amino acids peptides and proteins) Parasitology Intracellular |
| Zdroj: | Infection and Immunity. 75:1089-1098 |
| ISSN: | 1098-5522 0019-9567 |
| Popis: | A number of bacterial pathogens utilize the type III secretion pathway to deliver effector proteins directly into the host cell cytoplasm. Certain strains of Pseudomonas aeruginosa associated with acute infections express a potent cytotoxin, exoenzyme U (ExoU), that is delivered via the type III secretion pathway directly into contacting host cells. Once inside the mammalian cell, ExoU rapidly lyses the intoxicated cells via its phospholipase A 2 (PLA 2 ) activity. A high-throughput cell-based assay was developed to screen libraries of compounds for those capable of protecting cells against the cytotoxic effects of ExoU. A number of compounds were identified in this screen, including one group that blocks the intracellular activity of ExoU. In addition, these compounds specifically inhibited the PLA 2 activity of ExoU in vitro, whereas eukaryotic secreted PLA 2 and cytosolic PLA 2 were not inhibited. This novel inhibitor of ExoU-specific PLA 2 activity, named pseudolipasin A, may provide a new lead for virulence factor-based therapeutic design. |
| Databáze: | OpenAIRE |
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