Formyl peptide receptor-mediated proinflammatory consequences of peptide deformylase inhibition in Staphylococcus aureus.
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.
Cellular and Molecular Microbiology Division, Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Elfriede-Aulhorn-Strasse 6, 72076 Tübingen, Germany.
Diana
D
Mader
Marie-Joséphe
MJ
Rabiet
Francois
F
Boulay
Andreas
A
Peschel
D000581:Amidohydrolases / Q000037:antagonists & inhibitors*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors*; D039481:CD11b Antigen / Q000096:biosynthesis; D002118:Calcium / Q000378:metabolism; D002633:Chemotaxis; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D007249:Inflammation; D016209:Interleukin-8 / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology; D044042:Receptors, Formyl Peptide / Q000276:immunology* / Q000502:physiology*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology*
D001426:Bacterial Proteins; D039481:CD11b Antigen; D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D016209:Interleukin-8; D044042:Receptors, Formyl Peptide; D000581:Amidohydrolases; C084507:peptide deformylase; C010531:actinonin; D002118:Calcium