PhD project

Supervisor: Mathew Stracy

Antibiotics are a double-edged sword: they are crucial for treating ongoing 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. 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 mechanisms, such as conjugation. The behaviour of resistant strains and the level of horizontal gene transfer within the microbiota during treatment depends on the specific antibiotic, resistance mechanism, as well as the makeup of the other bacteria present in the microbiota.

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 spread within the microbiota?
• How does antibiotic-induced pathogen overgrowth and level of horizontal gene transfer differ between individuals?
• Can we engineer the microbiota to prevent the spread of resistance?

To achieve this, we will use a combination of in vitro and in vitro experimental approaches with synthetic and human-derived microbial communities. Microscopy methods will be used to understand the effect of antibiotics on the micro-scale biogeography of the microbiota. We will test approaches to modify the microbiota to minimize antibiotic-induced pathogen overgrowth or horizontal gene transfer.

Keywords:

• Microbiology, Evolution, Genetics, Molecular Biology 

Publications:

1. de Nies, L., Kobras, C.M. & Stracy, M. Antibiotic-induced collateral damage to the microbiota and associated infections. Nat Rev Microbiol (2023).
2. Stracy, M. et al., Minimizing treatment-induced emergence of antibiotic resistance in bacterial infections. Science 375, 889-894 (2022).