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«Analyse der kodierenden Nukleotidsequenz des 1 Megadalton extracellular matrix binding proteins von Staphylococcus epidermidis Dissertation zur ...»

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5 Zusammenfassung Staphylococcus epidermidis ist einer der häufigsten Erreger bei Fremdkörper-assoziierten Infektionen. Vor dem Hintergrund der unbefriedigenden präventiven, therapeutischen und diagnostischen Möglichkeiten besteht ein hohes Interesse an der Aufklärung der molekularen Pathogenese, um hierdurch neue Wege zur Bekämpfung von S. epidermidis Infektionen zu erkennen. Wichtigster Pathogenitätsfaktor von S. epidermidis ist seine Fähigkeit zur Ausbildung mehrlagiger Biofilme auf artefiziellen Oberflächen. Unabhängig vom interzellulären Polysaccharidadhäsin PIA ist bei dem hier untersuchten S. epidermidis Stamm 1585-Ra das Embp (extracellular matrix binding protein, Embp) am Prozess der Biofilmbildung beteiligt. S. epidermidis 1585-Ra produziert im Vergleich zum korrespondierenden Wildtypstamm 1585 Embp in großen Mengen. Durch Analyse des embp-Allels von S. epidermidis 1585-Ra, durch Sequenzierung und Bestimmung des Transkriptionsstart mittels 5´RACE konnte gezeigt werden, dass die Ursache für diese Überexpression in einer Insertion der Gene fmtC, msrA und msrR in embp liegt. Die Insertion hat zur Folge, dass bei S. epidermidis 1585-Ra der offene Leserahmen von embp geteilt wird, wobei die Basenpaare 18213 - 30612 in frame mit den msrR Nukleotiden 1 – 461 fusioniert vorliegen. Hierdurch kann das msrR-embp-Hybridgen unter Kontrolle des natürlichen msrR-Promoters exprimiert werden. Bei Analyse der von der Nukleotidsequenz abgeleiteten Aminosäuresequenz zeigte sich, dass Embp eine hochgradig modulare Struktur aufweist, die insbesondere durch FIVAR- und GA-Domänen bestimmt ist. Da Embp als interzelluläres Adhäsin fungiert, gibt es somit erstmalig Hinweis auf die konkrete Funktionalität dieser Domänen. Da Embp bei praktisch allen S. epidermidis Stämmen gefunden werden kann, stellt dieses Protein eine interessante Zielstruktur für die zukünftige Entwicklung innovativer präventiver oder therapeutischer Strategien zur Bekämpfung von S. epidermidis Infektionen dar.

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