Role of Charge Properties of Bacterial Envelope in Bactericidal Action of Human Group IIA Phospholipase A2against Staphylococcus aureus
| Autor: | Andreas Peschel, Michael H. Gelb, Jerrold P. Weiss, Tomaz Koprivnjak, Ning S. Liang |
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| Rok vydání: | 2002 |
| Předmět: |
Anions
Staphylococcus aureus Time Factors beta-Defensins Cell Survival Phospholipase medicine.disease_cause Group II Phospholipases A2 Models Biological Biochemistry Phospholipases A Cell membrane Cell wall chemistry.chemical_compound Phospholipase A2 Cell Wall Cations medicine Humans Molecular Biology Teichoic acid Alanine Dose-Response Relationship Drug biology Cell Membrane Cell Biology Lipid Metabolism biology.organism_classification Recombinant Proteins Anti-Bacterial Agents Phospholipases A2 medicine.anatomical_structure chemistry Mutagenesis Site-Directed biology.protein Calcium lipids (amino acids peptides and proteins) Chromatography Thin Layer Cell envelope Bacteria Protein Binding |
| Zdroj: | Journal of Biological Chemistry. 277:47636-47644 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m205104200 |
| Popis: | Mammalian Group IIA phospholipases A(2) (PLA(2)) potently kill Staphylococcus aureus. Highly cationic properties of these PLA(2) are important for Ca(2+)-independent binding and cell wall penetration, prerequisites for Ca(2+)-dependent degradation of membrane phospholipids and bacterial killing. To further delineate charge properties of the bacterial envelope important in Group IIA PLA(2) action against S. aureus, we examined the effects of mutations that prevent specific modifications of cell wall (dltA) and cell membrane (mprF) polyanions. In comparison to the parent strain, isogenic dltA(-) bacteria are approximately 30-100x more sensitive to PLA(2), whereas mprF(-) bacteria are3-fold more sensitive. Differences in PLA(2) sensitivity of intact bacteria reflect differences in cell wall, not cell membrane, properties since protoplasts from all three strains are equally sensitive to PLA(2). A diminished positive charge in PLA(2) reduces PLA(2) binding and antibacterial activity. In contrast, diminished cell wall negative charge by substitution of (lipo)teichoic acids with d-alanine reduces antibacterial activity of bound PLA(2), but not initial PLA(2) binding. Therefore, the potent antistaphylococcal activity of Group IIA PLA(2) depends on cationic properties of the enzyme that promote binding to the cell wall, and polyanionic properties of cell wall (lipo)teichoic acids that promote attack of membrane phospholipids by bound PLA(2). |
| Databáze: | OpenAIRE |
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