Engineering the microbiota to reduce the spread of antibiotic resistance
Antibiotics are crucial for the treatment of bacterial infections, but they can also cause significant collateral damage to the microbiota (de Nies et al. Nat Rev Microbiol. 2023). Antibiotics supress the growth of commensal microorganisms and at the same time select for drug-resistance. Individuals are often benignly colonized with resistant potential pathogens persisting at low levels within their microbiota, such as extra-intestinal pathogenic Escherichia coli (ExPEC). Antibiotics can lead to overgrowth of these resistant pathogens, facilitating their spread within and between individuals (Stracy et al. Science. 2022).Antibiotics can also lead to resistance genes spreading between bacteria within the microbiota through various horizontal gene transfer (HGT) mechanisms.
This overall aim of this project is to answer the important questions:
- What are the key factors that determine the level of antibiotic-induced resistance overgrowth/spread within the microbiota?
- How does antibiotic-induced pathogen overgrowth and level of HGT differ between individuals?
- Can we engineer the microbiota to prevent the spread of resistance?
To achieve this, we will use experimental approaches with synthetic and human-derived microbial communities as well as developing microscopy methods to understand the effect of antibiotics on the micro-scale biogeography of the microbiota. We will test approaches to modify the members of the microbiota to minimize antibiotic-induced pathogen overgrowth or HGT.