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Molecular mechanisms of microbiota-mediated colonization resistance against intestinal outgrowth of multidrug-resistant Enterobacteriaceae (E. coli, K. pneumoniae) and enterococci

Group and collaboration

Rob Willems & Marc Bonten - Department of Medical Microbiology University Medical Center Utrecht
PhD student: Paul Stege

Project description

This project aims to decipher the processes and molecular mechanisms that contribute to colonization resistance against high density colonization of multidrug resistant (MDR) Enterobacteriaceae and enterococci and the consequences of intestinal outgrowth of MDR Enterobacteriaceae and enterococci on pathogen-host cross-talk when colonization resistance is impaired. This will elucidate the mechanistic foundations, and physiological significance, of beneficial or pathogenic relationships between the gut microbiota and their hosts.

Tasks

  1. Metagenomic profiling of the microbial composition of hospitalized patients with and without MDR Enterobacteriaceae and Enterococcus acquisition and high density intestinal colonization.
  2. Using metabolomics approaches to define the functional status of the patient-associated microbial ecosystems and bacterial community–host interaction with and without MDR Enterobacteriaceae and Enterococcus acquisition and high density intestinal colonization.
  3. Use the data from task-1 and -2 to study in detail inter-bacterial and bacterial-host cross-talk using human intestinal organoids.
  4. Study host-specificity of inter-bacterial and bacterial-host cross-talk using different combinations of human and animal-derived strains in in human and animal-derived organoids.

Complex Systems & Metagenomics is the overarching theme for more than 10 PhD tracks in NCOH projects to create new interdisciplinary, inter-thematic, and inter-institutional research collaborations.

PhD student interview

Interview: Functional consequences of gut microbiome and resistome dynamics

‘During my bachelor I started learning how bacteria play a role in our environment, but also in our bodies. I was amazed to learn that bacteria are present in such large numbers and with high diversity, thereby forming complex ecosystems. Nevertheless, we know little about the microbial interactions that take place and how this affects... More