Objective Clostridium difficile is a Gram-positive, anaerobic bacterium that relies on the disturbance of the normal gut microbiota to colonize the human intestinal tract and cause infection and disease. In the last decade new strains of C. difficile have emerged to cause outbreaks of increased disease severity and higher recurrence and mortality rates. C. difficile infection (CDI) is becoming refractory to the conventional antibiotic treatments and probiotic-based approaches are viewed as promising alternative therapies to effectively treat CDI. The development of such bacterial-based treatments requires the identification of the mechanisms by which the commensal members of the gut microbiota are able to eradicate C. difficile, as well as of the identity of the members of the gut microbiota that orchestrate those mechanisms. Since nutrient competition is an important mechanism by which the colonic microbiota suppresses the growth of many enteric pathogens, I focus here on competition for limited nutrient sources, such as the gut mucosal sugars N-acetylglucosamine (GlcNAc) and sialic acid, as a mechanism by which the members of the gut microbiota can eradicate C. difficile. I will investigate in detail the importance of GlcNAc catabolism, both alone and in combination with the catabolism of sialic acid, for C. difficile expansion in the gut. Furthermore, by combining stable isotope probing (SIP) and fluorescence in situ hybridization (FISH) with high resolution secondary ion mass spectrometry (NanoSIMS) I propose to identify commensal members of the gut microbiota that can efficiently catabolize these mucosal carbohydrates in vivo and to evaluate the ability of the identified organisms to outcompete C. difficile. Thus, this work will contribute to elucidate the mechanisms by which the gut microbiota prevents C. difficile colonization and to identify members of the gut microbiota that can be the basis for an effective, safe and standardized treatment to cure CDI. Fields of science natural sciencesbiological sciencesmicrobiologybacteriologymedical and health sciencesbasic medicineimmunologymedical and health sciencesclinical medicinetransplantationnatural scienceschemical sciencesanalytical chemistrymass spectrometrynatural sciencesphysical sciencesopticsspectroscopy 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 UNIVERSITAT WIEN Net EU contribution € 166 156,80 Address Universitatsring 1 1010 Wien Austria See on map Region Ostösterreich Wien Wien 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 Other funding € 0,00
