Obiettivo Bacterial pathogens possess the ability to adapt rapidly to changing environmental conditions which is especially apparent in the hospital setting where bacteria acquire antibiotic resistances readily. Besides well studied mechanisms such as horizontal gene transfer bacteria can alter the genetic material by acquiring gen duplications and amplifications (GDA). Exemplarily an improved gene dosage of a minor resistance determinant can lead to increased resistance to antibiotics. Due to the difficulties in their detection GDAs are almost exclusively studied in model organisms and neglected in natural populations of clinically relevant species such as Staphylococcus aureus. Accordingly many important questions about the frequency and clinical importance of GDAs remain unanswered. State of the art sequencing technologies enable the identification of GDAs by analysis of the coverage scaffold and groundbreaking experiments using 387 USA300 genome sequences showed promising results regarding putative copy number variation of virulence factors. We will extend the GDA analysis to ca. 1200 already available EMRSA15 sequences. This will enable a comprising analysis of gen copy number variation in clinical isolates and might allow identifying genomic regions under strong evolutionary pressure during infection. We will optimize experimental setups for the rapid validation of GDAs by qPCR and develop techniques to study the effects of GDAs in S. aureus. Furthermore we will sequence a selection ca. 70 S. aureus isolates causing chronic infections in patients suffering from cystic fibrosis (CF). This will enable us to optimize the detection of GDAs by NGS and will allow investigating the role of GDAs during adaption to the complex environment within the CF-lung. This project will show new avenues to extract additional valuable biological information from NGS data and will investigate the importance of GDAs during the adaption of S. aureus to the hospital setting and to the CF-lung. Campo scientifico medical and health sciencesmedical biotechnologygenetic engineeringgene therapynatural sciencesbiological sciencesmicrobiologybacteriologymedical and health sciencesbasic medicineimmunologymedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantibioticsmedical and health sciencesbasic medicinepharmacology and pharmacydrug resistanceantibiotic resistance Programma(i) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Argomento(i) MSCA-IF-2014-EF - Marie Skłodowska-Curie Individual Fellowships (IF-EF) Invito a presentare proposte H2020-MSCA-IF-2014 Vedi altri progetti per questo bando Meccanismo di finanziamento MSCA-IF-EF-ST - Standard EF Coordinatore EBERHARD KARLS UNIVERSITAET TUEBINGEN Contribution nette de l'UE € 171 460,80 Indirizzo GESCHWISTER-SCHOLL-PLATZ 72074 Tuebingen Germania Mostra sulla mappa Regione Baden-Württemberg Tübingen Tübingen, Landkreis Tipo di attività Higher or Secondary Education Establishments Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale € 171 460,80