Timeline

2019 - 2023

Group and collaboration

Prof. Dr. T. Hankemeier and Dr. J.G.C. van Hasselt, Leiden University - LACDR
PhD student: Maik Kok

Project description

Environmental pathogen Pseudomonas aeruginosa is known for its advanced mechanisms for antibiotic survival once it colonizes the host, especially in currently incurable lung infections of cystic fibrosis patients. Successful colonization and persistence during antibiotic treatment in this specific niche requires extensive metabolic flexibility. Bacterial metabolism has proved to be a pivotal factor for phenotypical adaptions to withstand antibiotic therapy, such as biofilm and persister cell formation. Moreover, mutations resulting in antibiotic resistance entail several metabolic constraints. However, the exact metabolic changes and the role of the host microenvironment in antibiotic survival is still poorly understood. In this project, we will focus on nutritional cues in the host microenvironment inducing antibiotic survival by biofilm or persister formation and supporting resistance selection.

Tasks and aims

1. Uncovering nutritional cues in modified artificial lung sputum medium related to antibiotic survival in bacterial biofilms and persister cells.
2. Investigate bacterial metabolic adaptions during the evolution towards antibiotic resistance.
3. Development of an in vivo representative lung-on-a-chip cell culture model to study host-pathogen metabolic interactions.
4. Analysis of metabolic changes will be done with mass spectrometry based metabolomics. Ameliorated by miniaturization of mass spectrometry based methods to analyze volume limited samples.