Formyl peptide receptor-mediated proinflammatory consequences of peptide deformylase inhibition in Staphylococcus aureus. 2010

Diana Mader, and Marie-Joséphe Rabiet, and Francois Boulay, and Andreas Peschel
Cellular and Molecular Microbiology Division, Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Elfriede-Aulhorn-Strasse 6, 72076 Tübingen, Germany.

The biosynthesis of proteins with N-terminal formylated methionine residues and subsequent protein deformylation are unique and invariant bacterial processes. They are exploited by the capacity of the human innate immune system to sense formylated peptides (FPs) and targeted by the deformylation-blocking antibiotic actinonin. We show that human polymorphonuclear leukocytes respond via the formyl peptide receptor (FPR) with increased calcium ion fluxes, chemotactic migration, IL-8 release, and CD11b upregulation to the human pathogen Staphylococcus aureus upon actinonin treatment. These data underscore the crucial role of bacterial FPs in innate immunity and indicate that deformylase inhibition may have considerable proinflammatory consequences.

UI MeSH Term Description Entries
D007249 Inflammation A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. Innate Inflammatory Response,Inflammations,Inflammatory Response, Innate,Innate Inflammatory Responses
D009504 Neutrophils Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. LE Cells,Leukocytes, Polymorphonuclear,Polymorphonuclear Leukocytes,Polymorphonuclear Neutrophils,Neutrophil Band Cells,Band Cell, Neutrophil,Cell, LE,LE Cell,Leukocyte, Polymorphonuclear,Neutrophil,Neutrophil Band Cell,Neutrophil, Polymorphonuclear,Polymorphonuclear Leukocyte,Polymorphonuclear Neutrophil
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D002633 Chemotaxis The movement of cells or organisms toward or away from a substance in response to its concentration gradient. Haptotaxis
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006877 Hydroxamic Acids A class of weak acids with the general formula R-CONHOH. Hydroxamic Acid,Acid, Hydroxamic,Acids, Hydroxamic
D000581 Amidohydrolases Any member of the class of enzymes that catalyze the cleavage of amide bonds and result in the addition of water to the resulting molecules. Amidases,Amidohydrolase
D001426 Bacterial Proteins Proteins found in any species of bacterium. Bacterial Gene Products,Bacterial Gene Proteins,Gene Products, Bacterial,Bacterial Gene Product,Bacterial Gene Protein,Bacterial Protein,Gene Product, Bacterial,Gene Protein, Bacterial,Gene Proteins, Bacterial,Protein, Bacterial,Proteins, Bacterial
D013211 Staphylococcus aureus Potentially pathogenic bacteria found in nasal membranes, skin, hair follicles, and perineum of warm-blooded animals. They may cause a wide range of infections and intoxications.

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