Kurzfassung

Photobacterium damselae subsp. damselae (Pdd), formerly Vibrio damsela, is a pathogen of marine animals, which causes hyper-aggressive wound infections and hemorrhagic septicemia in humans. Due to global ocean warming pathogenic Vibrio species are spreading world-wide; the most dramatic temperature increase is being recorded in the Baltic Sea, where fatal infections by Pdd-related Vibrio vulnificus have been observed. Recently a new virulence plasmid of Pdd was discovered and it was...Photobacterium damselae subsp. damselae (Pdd), formerly Vibrio damsela, is a pathogen of marine animals, which causes hyper-aggressive wound infections and hemorrhagic septicemia in humans. Due to global ocean warming pathogenic Vibrio species are spreading world-wide; the most dramatic temperature increase is being recorded in the Baltic Sea, where fatal infections by Pdd-related Vibrio vulnificus have been observed. Recently a new virulence plasmid of Pdd was discovered and it was demonstrated that plasmid-encoded hemolysins are important virulence factors in both fish and mice. In a joint effort with the laboratory of Prof. Husmann we characterized one of two similar new hemolysins of Pdd and investigated the interaction of Pdd with mammalian cells in vitro. This led to the fortuitous observation that expression of hemolysins strongly promotes the association of bacteria with target cells. Follow up on this unexpected finding showed that this phenomenon was observable with various hemolysins, bacteria and cell types. Association of pathogens with host cells is a fundamental step in the course of most infectious diseases, and hemolysins are produced by the majority of pathogenic bacteria. It is planned to include endothelial cells in our studies because they are obvious targets in hemorrhagic septicemia. Mechanistically, two potential explanations for hemolysin-dependent bacterial association with target cells have to be considered: first, increased adherence, second, chemotactic targeting to host cells: Nutrients and ions released by damaged cells are expected to generate gradients along which motile bacteria might travel to the source. The “ECHO (Exotoxin-dependent chemotactic orientation) concept” will enable us to analyze in detail the emerging novel function of hemolysins, and to clarify how it relates to the foudroyant course of disease caused by Pdd. In doing so we would establish a new experimental paradigm for studying the interaction of a gram negative bacterium with vascular endothelium. Because such interactions are likely to impact pathogenesis, the model should also aid in the development of approaches to analyze and fight the direct consequences of gram-negative sepsis, which ranks among the most frequent, life-threatening conditions in our hospitals.
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