Diese Daten zeigen, dass die vier untersuchten Gene topB1, rfaE, pgm und EAMY_2231 Einfluss auf die Herstellung oder den Export mehrere Oberflächenstrukturen wie LPS, EPS oder bakterieller Cellulose haben und somit multiple Phagenresistenz vermitteln. Um zu untersuchen, ob diese Gene und deren Genprodukte ein Risiko für die Behandlung von E. amylovora mittels Phagen Cocktails darstellen, wurden die Mutanten auf allfällige Fitness Einbußen untersucht. Im Gegensatz zum Wildtype waren Mutanten mit

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... topB1, rfaE-oder pgm-Deletionen nicht in der Lage, die Blüten zu kolonisieren und zu infizieren. Da EPS und vor allem Amylovoran essentiell sind, um das Bakterium an die Pflanzenoberfläche anzuhaften, das pflanzliche Immunsystem zu umgehen und als Virulenzfaktor fungieren, kann davon ausgegangen werden, dass die bei diesen Mutanten beobachtete starke Verringerung der EPS-Produktion, für diesen Phänotyp verantwortlich ist. Für den Fall, dass ein Bakterium tatsächlich die Strategie eines dieser Gene zu modifizieren anwendet um einen Phagen Angriff vorzubeugen, würde diese Veränderung den Keim avirulent machen. Somit würde die Pflanze den Befall überleben. Bakterien mit EAMY_2231-Modifikation hingegen, generierten gleich starke Krankheitssymptome wie der Wildtype. Unsicher ist, ob die in vitro beobachtete EAMY_2231-Modifikation auch nach einer Y2-Exposition in planta auftreten kann. Für den Fall, dass solche Mutanten aus infizierten Blüten, die mit Y2 behandelt wurden, isoliert werden können, sollte der Phage nicht in einen Phagencocktail gegen E. amylovora integriert werden. Die entsprechenden Anpassungen des Phagencocktails sollten sicherstellen, dass das Risiko der Resistenzentwicklung nach einer Phagenbehandlung minimiert wird. reaction in non-host plants (14). These proteins include the harpins HrpN and HrpW, which are released into the apoplast of the plant tissue (15). There, HrpN, which is essential to generate full virulence, potentially forms pores in the plant plasma membrane and facilitates translocation of DspA/E into the plant cell (16). The injected disease specific effector protein DspA/E will interfere with plant signalling and induces cell death (17). The expression of these hrp genes is tightly regulated. Expression is only induced under certain conditions such as low nutrients or low pH (18). In response to these environmental factors, the genes hrpS, hrpX 1.1.2. The disease Members of the Rosaceae family can be infected by fire blight (5). The economically most valuable plants in this family are apples and pears. First observations of fire blight symptoms were made in 1780 in the Hudson valley of New York state (36). From there the disease spread slowly all over the entire country. With increasing human mobility and trade, fire blight started to spread to neighbouring countries at the beginning of the 20 th century. Around 1950, first fire blight cases were observed in Europe, possibly due to infested wood or trees imported from Northern America (5). Until today, the disease has spread to multiple countries on all continents. Bacteriophages History Bacteriophages are viruses exclusively infecting bacteria. With an estimated number of 10 31 (72), phages pose the most abundant biological entity on earth and outnumber bacteria by at least tenfold (73). Phages are ubiquitous and can readily be isolated from lakes, soils, sediments, biofilms and microfloras of humans, animals and plants. Since phages are dependent on their hosts' metabolism for reproduction, they can often be found in close proximity to them (74). Phages were first identified in 1915 by Frederick Twort, who described the phenomenon of glassy transformation of bacteria (75). In 1917, Felix d'Hérelle independently discovered these "bacteria eating microorganisms", which could lyse bacteria in liquid and produce plaques on agar plates and named them bacteriophage. He realised their potential and investigated them as remedy against a collection of bacterial pests (76, 77). The identification of penicillin in 1928 by Alexander Fleming (79), however, diverted the focus from phage therapy and shifted it to the newly discovered antibiotics (80). Eastern European countries with hotspots in Tbilisi (Georgia) and Wroclaw (Poland) maintained an interest in advancing phage therapy as treatment against pathogenic bacteria. In western countries, however, the potential of phage therapy sunk into oblivion. Instead of phages as antimicrobial agents, investigating them as model organisms became more popular. Several studies used phages to elucidate the basic principles of life including the nature and function of DNA and the genetic code, gene expression or studies on cell regulation (78). Whole genome The abortive infection system (abi), however, is fatal for the infected bacteria. These abi systems are diverse in sensing and reacting to phage infection. Once activated, the infected bacterium destroys itself thereby preventing phage proliferation. This sacrifice guarantees survival of the surrounding bacterial population (113). Phage resistance is observed to be either transient or permanent (118, 119) . Permanent resistance against phages can involve spontaneous genetic mutations. Such mutations can possibly impact fitness or virulence of