Targeting lipopolysaccharides by the nontoxic polymyxin B nonapeptide sensitizes resistant Escherichia coli to the bactericidal effect of human neutrophils
| Autor: | Friedrich Grimminger, Sabine Hombach-Klonisch, Frank Rose, Werner Seeger, Ladislau Kiss, Kay U. Heuer, Ulf Sibelius |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Lipopolysaccharides
Lipopolysaccharide Leukotriene B4 Neutrophils Cell Respiration Biology In Vitro Techniques medicine.disease_cause Phosphatidylinositols Microbiology chemistry.chemical_compound Phagocytosis medicine Escherichia coli Immunology and Allergy Humans Opsonin Polymyxin B Dose-Response Relationship Drug Pancreatic Elastase Chemotaxis Elastase Drug Resistance Microbial Lipid Metabolism Complement system Anti-Bacterial Agents Infectious Diseases chemistry Bacterial outer membrane medicine.drug |
| Zdroj: | The Journal of infectious diseases. 182(1) |
| ISSN: | 0022-1899 |
| Popis: | The nonapeptide of polymyxin B (PMBN) has been reported to sensitize various pathogenic gram-negative bacteria to the direct bactericidal effect of human serum. To investigate the impact of PMBN on human neutrophil‐effected killing of the serum- and phagocytosis-resistant Escherichia coli strains C14 and O111, serum was coapplied with PMBN or with neutrophils, but this did not result in decreased numbers of viable bacteria. In contrast, the most potent bacterial killing occurred in the presence of neutrophils plus serum components plus PMBN. The effect of this on E. coli C14 was the appearance of inositol phosphates, diacylglycerol, respiratory burst, elastase liberation, and generation of lipid mediators (leukotriene B4, 5-HETE, and platelet-activating factor). Strong neutrophil activation required early, but not late, complement components and was blocked by inhibition of phagocytosis with cytochalasin D. PMBN seems to cause dramatic support of natural host defense by complement-dependent sensitization of E. coli to the bactericidal efficacy of human neutrophils. Escherichia coli is a clinically relevant human pathogen. It causes severe infection, sepsis, and sepsis-related organ injury, which is an important cause of death in critically ill patients [1, 2]. Its virulence is dependent on several factors. First, Oantigenic lipopolysaccharides (LPSs) of the outer membrane, liberated upon bacterial breakdown, are potent inductors of host inflammatory events, linked to the clinical appearance of sepsis and septic shock [3]. Second, »50% of E. coli isolates causing extraintestinal infections in humans secrete a-hemolysin, a proteinaceous, pore-forming, microbial a-toxin, which attacks immunocompetent and endothelial cells and triggers cell death and inflammatory processes [4‐7]. Third, many strains of E. coli are resistant to the lytic action of the complement cascade and to phagocytosis by leukocytes. Such resistance of bacteremic E. coli has been linked to the coating of the outer membrane with long hydrophilic polysaccharide structures, as encountered in the smooth strains, and to the presence of the low immunogenic K1 capsule [8‐11]. Activation of the complement cascade is thereby suppressed, with the opsonic C3b and the lytic terminal complex occurring less often. In addition, the access of this lytic complement complex to the |
| Databáze: | OpenAIRE |
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