Objective 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. Fields of science 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 Programme(s) 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 Topic(s) MSCA-IF-2014-EF - Marie Skłodowska-Curie Individual Fellowships (IF-EF) Call for proposal H2020-MSCA-IF-2014 See other projects for this call Funding Scheme MSCA-IF-EF-ST - Standard EF Coordinator EBERHARD KARLS UNIVERSITAET TUEBINGEN Net EU contribution € 171 460,80 Address GESCHWISTER-SCHOLL-PLATZ 72074 Tuebingen Germany See on map Region Baden-Württemberg Tübingen Tübingen, Landkreis Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 171 460,80