Projektbeschreibung
Kommensale Bakterien als Therapieoption gegen antibiotikaresistente Krankheitserreger
Persistierende latente (ruhende) Zellen in Mikrobenpopulationen entwickeln eine hohe Toleranz gegen Antibiotika und geben diese sogenannten antimikrobiellen Resistenzen (AMR) über mobile genetische Elemente in der Population weiter. Einen wichtigen Beitrag zur Abwehr von Krankheitserregern leisten dabei verschiedenste kommensale Bakterien, die auf der Haut und Schleimhaut siedeln. Sie hemmen die Vermehrung von Krankheitserregern in den Atemwegen, stimulieren durch Signale die Mikrobenabwehr des Körpers, konkurrieren um Nährstoffe und Platz und aktivieren Immunreaktionen. Das über die Marie-Skłodowska-Curie-Maßnahmen finanzierte Projekt PERSIST kombiniert Omics-Technologien mit Mausmodellen und Modellen für Krankheiten auf der Suche nach persistierenden Kommensalen, die so eingesetzt werden könnten, dass sie persistierende pathogene Bakterien verdrängen. Ziel des Projekts sind neue Behandlungsoptionen gegen persistierende Krankheitserreger und horizontal übertragene AMR.
Ziel
Persisters are transiently non-growing bacteria cells that evade antibiotic treatment and immune response. Persisters have been associated with antibiotic treatment failure and the spread of antibiotic-resistance (AMR) through mobile genetic elements. Consequently, persisters contribute significantly to the morbidity and mortality of bacterial infections, and increased medical costs. Although it is known that many pathogenic bacteria are able to form persisters, the occurrence of persistence among commensal bacteria is yet unexplored. This project aims to identify and exploit commensal persisters able to antagonise and displace pathogenic persisters, offering opportunities for the development of innovative treatment options to arrest both the relapse of persistent infections and the horizontal transfer of AMR. To this effect, I will use a combination of cutting-edge omics-based tools, in vivo murine models and the well-established and relevant Salmonella enterica serovar Typhimurium enteric model pathogen. After identifying commensal species forming persisters (WP1), I will assess the ability of these persisters to compete with Salmonella persisters during infection (WP2) and to arrest in vivo horizontal gene transfer from Salmonella persisters to intestinal microbiota (WP3). My goal is to become a leading academic scientist in the intertwining fields of antibiotic-resistance and antibiotic-persistence, with emphasis on the involvement of persister cells in the maintenance and spread of mobile genetic elements encoding AMR. The state-of-the-art computational and experimental training at the pioneering groups of in vivo persister biology at Harvard Medical School (HMS) in USA and of genome spatial organization at the Institut Pasteur (IP) in France will be instrumental towards achieving my goal. Apart from empowering my career track, this fellowship will foster future collaborations between HMS and IP, and promote transfer of knowledge in Europe.
Wissenschaftliches Gebiet
- natural sciencesbiological sciencesmicrobiologybacteriology
- medical and health sciencesbasic medicineimmunology
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantibiotics
- medical and health sciencesbasic medicinepharmacology and pharmacydrug resistanceantibiotic resistance
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Aufforderung zur Vorschlagseinreichung
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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Koordinator
75724 Paris
Frankreich