Molecular mechanisms of microbiota-mediated colonization resistance against intestinal outgrowth of multidrug-resistant Enterobacteriaceae (E. coli, K. pneumoniae) and enterococci
Group and collaboration
Collaboration: Rob Willems & Marc Bonten (Department of Medical Microbiology University Medical Center Utrecht)
PhD student: Paul Stege
Dissertation: Making yourself at home in the intestinal tract – Dynamics of the microbiome, resistome and host-pathogen interactions
Date: 9 November 2022
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.
- Metagenomic profiling of the microbial composition of hospitalized patients with and without MDR Enterobacteriaceae and Enterococcus acquisition and high density intestinal colonization.
- 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.
- Use the data from task-1 and -2 to study in detail inter-bacterial and bacterial-host cross-talk using human intestinal organoids.
- 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.
PhD student interview
‘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 us.’
The gut microbiome forms a reservoir for opportunistic pathogens as well as for antimicrobial resistance genes. This finding is important because it offers a deeper insight in the dynamics and mechanism of antimicrobial resistance development. This project – supported by a grant from the Netherlands Centre for One Health – was performed by Paul Stege who defended his PhD thesis on November 9, 2022 at Utrecht University.