1. Serratia type pore forming toxins.
- Author
-
Hertle R
- Subjects
- Animals, Bacterial Adhesion, Bacterial Toxins chemistry, Bacterial Toxins classification, Bacterial Toxins genetics, Bacterial Toxins pharmacology, Cell Membrane drug effects, Cell Membrane Permeability drug effects, Epithelial Cells drug effects, Erythrocytes drug effects, Eukaryotic Cells drug effects, Fibroblasts drug effects, Gram-Negative Bacteria genetics, Gram-Negative Bacteria physiology, Hemolysin Proteins genetics, Hemolysin Proteins pharmacology, Hemolysin Proteins physiology, Humans, Membrane Lipids metabolism, Operon, Opportunistic Infections blood, Opportunistic Infections microbiology, Phospholipids metabolism, Prokaryotic Cells drug effects, Rats, Serratia Infections blood, Serratia Infections microbiology, Serratia marcescens genetics, Serratia marcescens pathogenicity, Species Specificity, Virulence, Bacterial Proteins, Hemolysin Proteins chemistry, Serratia marcescens chemistry
- Abstract
The Serratia marcescens hemolysin represents a new type of hemolysin and has been studied in great molecular detail with regard to structure, activation and secretion. It has nothing in common with the pore forming toxins of E. coli type (RTX toxins), the Staphylococcus aureus alpha-toxin or the thiol activated toxin of group A beta-hemolytic streptococci (Streptolysin O). Studies on erythrocytes, eukaryotic cells and artificial black lipid membranes, have shown that the mechanism of pore formation of ShlA is different form other pore forming toxins. The S. marcescens hemolysin proteins ShlB and ShlA exhibit protein sequence homologues in Proteus mirabilis, Haemophilus ducreyi, Edwardsiella tarda and Erwinia chrysantemi. Furthermore, sequence motifs present in ShlA and Shlb have been shown to be important for activity and secretion of the S. marcescens hemolysin. Thus, the S. marcescens hemolysin forms the prototype of a new class of hemolysins and of a new secretory mechanism. The uniqueness of this new mechanism is underlined by the fact that activation of ShlA by ShlB strictly requires phosphatidylethanolamine as a cofactor. New data implicate a conformational change in ShlA during activation. In addition, ShlA not only forms pores in erythrocytes but also in fibroblasts and epithelial cells. The cytotoxic action of ShlA is mainly determined by lysis of infected cells in vitro. In sublytic doses, as will normally be the situation in vivo, ShlA exerts additionally effects which are currently under investigation. The knowledge of the structure, activation, secretion and mode of action of S. marcescens hemolysin has implications for proteins, related in sequence or in mode of secretion and activation.
- Published
- 2000
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