Outer membrane protein A deficient Escherichia coli activates neutrophils to produce superoxide and shows increased susceptibility to antibacterial peptides.
The outer membrane protein A (OmpA) of Gram-negative bacteria has been ascribed multiple functions including maintenance of structural membrane integrity and porin activity. OmpA has also been implicated in various host defense processes in that it contributes to bacterial serum resistance and activates certain immune cells. Recently, OmpA was shown to be the molecular target for neutrophil elastase (NE), and Escherichia coli mutants lacking OmpA were resistant to the bactericidal effects of NE. In addition to NE, neutrophils use a variety of other antibacterial effector molecules such as oxygen radicals and bactericidal peptides or proteins. The aim of this study was to investigate the role of E. coli OmpA regarding susceptibility to other neutrophil-derived defense systems. We found that OmpA-deficient (OmpA(-)), but not wild-type isogenic, E. coli activated human neutrophils to produce oxygen radicals intracellularly. This activation was found to require an intact neutrophil cytoskeleton but was independent of bacterial phagocytosis. Furthermore, we found that the OmpA(-) strain was more susceptible to membrane-acting bactericidal peptides than the wild-type strain, although the susceptibility to different oxygen radicals was independent of the presence of OmpA. Taken together, these data suggest an important role for OmpA in the context of bacteria vs. host interactions.
Fu
Huamei
H
Department of Rheumatology and Inflammation Research, University of Göteborg, Gothenburg, Sweden.
Belaaouaj
Abderr Azzaq
AA
Dahlgren
Claes
C
Bylund
Johan
J
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000502:physiology*; D003571:Cytochalasin B / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects / Q000502:physiology; D047630:Depsipeptides; D004926:Escherichia coli / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D008826:Microbial Sensitivity Tests; D019255:NADPH Oxidases / Q000378:metabolism; D018375:Neutrophil Activation / Q000502:physiology*; D009504:Neutrophils / Q000201:enzymology / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000494:pharmacology; D010587:Phagocytosis / Q000502:physiology; D017382:Reactive Oxygen Species / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D001425:Bacterial Outer Membrane Proteins; D047630:Depsipeptides; D010456:Peptides, Cyclic; D017382:Reactive Oxygen Species; C057531:jasplakinolide; D013481:Superoxides; C078167:OMPA outer membrane proteins; D003571:Cytochalasin B; D019255:NADPH Oxidases