How repeatable is the evolution of antibiotic resistance in different bacterial habitats?

Bacterial resistance to antibiotics is a threat to human health. A lack of effective antibiotics poses a direct threat in the form of an inability to cure life-limiting or life-threatening infections, and also an indirect threat to health because without antibiotics, we could not carry out medical treatments that leave patients with an increased risk of infection (e.g. surgery, transplants, chemotherapy).

If we can better understand how bacterial populations evolve resistance to antibiotics - what genetic mutations are involved, how fast resistance arises, whether resistance has any knock-on effects on bacterial susceptibility to other drugs - we will be better positioned to use antibiotics effectively - i.e. to choose the right drugs and the right treatment patterns (how much to prescribe, how often) so it is harder for the bacteria to become resistant.

To understand resistance evolution, scientists carry out experiments culturing bacteria over many generations in the presence of antibiotics to see how the population changes. Most of these experiments are carried out in standard laboratory growth media, which are designed to allow bacteria to grow very rapidly rather than being designed to mimic the environments within the body where pathogenic bacteria grow. This is a problem. The different environments at distinct infection sites, such as nutrient availability, oxygen availability, and stress imposed by the host immune system, could all affect how easily resistance evolves, what mutations are naturally selected for, and how resistance changes bacterial physiology.

In this project, I will study how bacteria that can infect multiple body sites (P. aeruginosa and E. coli) evolve antibiotic resistance in conditions that mimic infections of the respiratory, urinary tract or wounds. My work will help improve strategies the use of existing antibiotics, and provide ways to test how easily bacteria can evolve resistance to novel antibiotics.