Microbial Adaptation to Antibiotic Treatment Both in the Lab and the Clinic

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Antibiotics negatively effect bacterial growth and clear infection, hence why they are used therapeutically. Consequently, there is a focus on the effects that antibiotics have on the early stages of microbial growth, with standardised antibiotic susceptibility tests constrained to measure growth over hours, whilst infections can last for years. It is fundamental to our understanding of antibiotic treatment that we measure the effects that these drugs have on all stages of microbial life and death. Trade-offs are ubiquitous at all scales of life and are defined as the fitness costs experienced by an organism when a beneficial change in one trait is linked to a detrimental change in another. In particular, bacteria are subject to a growth-longevity trade-off, whereby slower growth results in accelerated death and rapid growth is detrimental to longevity. Certain antibiotics purposefully slow down growth rates, however the impact on bacterial longevity is unknown. This project will therefore seek to explore the effects that antibiotics have on bacterial death phase using a combination of evolutionary experiments and whole genome sequencing. Finally, there are a plethora of studies investigating microbial adaptation towards antibiotics within the laboratory environment, and yet our understanding of microbial adaptation within the human body is limited. Using Nanopore sequencing, we will characterise the within-patient genome-wide adaptation to repeated antibiotic treatment during chronic infections. This will develop our understanding of how pathogens evolve over long timescales within the human body, and more specifically the genetic pathways to antibiotic resistance.