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Project

Importance of Salmonella biofilm exopolymeric substances (EPS) during gut colonization and invasion — potential of EPS inhibition as an evolutionary robust antimicrobial strategy

Foodborne illnesses remain a significant global public health problem with large economic consequences, despite the strict regulations regarding food safety. Salmonella represents the most common cause of bacterial foodborne outbreaks. We hypothesize that the publicly available exopolymeric substances (EPS) of the biofilm matrix made by this pathogen play an important role in gut colonization and invasion. EPS are therefore considered as interesting novel and evolutionary robust antimicrobial targets. Our hypothesis is based on preliminary research in our lab that observed reduced colonization of the ileum, liver and spleen by EPS deletion mutants in a murine model. The project aims to investigate the potential importance of Salmonella EPS in (i) surviving the harsh conditions in the gastrointestinal tract, (ii) modulating the host immune response, and (iii) providing tolerance against the immune response, (iv) competition by the gut microbiome, or (v) antibiotics. In house developed EPS inhibitors will be selected based on low cytotoxic and high inhibiting activity. Evolution experiments in a murine model will validate in vitro results on the evolutionary robustness against resistance of this new antimicrobial strategy. If successful, this project will provide in vivo proof of concept for evolution-proof drugs targeting public traits, potentially leading to a major breakthrough in the search for novel antimicrobial strategies with less risk of resistance development.

Date:3 Sep 2021 →  Today
Keywords:evolution-proof antimicrobial drugs, Exopolymeric substance inhibitors, Salmonella gut infections
Disciplines:Clinical microbiology
Project type:PhD project