Profiling evolutionary landscapes underlying drug resistance

Rachel Hickman

Research output: Book/ReportPh.D. thesisResearch

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Abstract

Bacteria have existed on earth for 3.5 million years and their ability to evolve has allowed for their survival in almost all global niches. Bacteria evolve and adapt easily due to their short generation times, plastic genomes, acquisition (external) DNA and their ability to form protective bacterial communities i.e. biofilms or dormant metabolic states.
Antibiotic drugs are currently our best medicine to treat (against) bacterial pathogens due to antibiotics unique properties of being small molecules that are soluble and act systemically. These qualities allow for many modern medical procedures to occur due to antibiotics preventative/ prophylactic and therapeutic qualities.
Despite bacterial antibiotic resistance mechanisms always being present in nature, the overuse and misuse of antibiotics by humans are accelerating the rise and dissemination of bacterial antibiotic resistance. Bacterial antibiotic resistance is global threat to public health; especially because of lack of new drugs. It has been highlighted that understanding antibiotic resistance by further elucidating mechanisms of evolution, molecular mechanisms of action and reservoirs of resistance are essential Therefore, the work involved in this PhD thesis, examines the evolution of antibiotic resistance in bacterial populations.
Two main studies were performed: the first to elucidate the molecular mechanisms of collateral sensitive drug pairs and collateral resistance drug pairs in adaptation of Escherichia coli populations; and the second exploring mutant variant dynamics in cystic fibrosis lung, by analyzing sputum samples from chronic carriers of Pseudomonas aeruginosa undergoing antibiotic treatment.
Both studies explore the trajectories of antibiotic resistance within bacterial populations: the first study by exploring antibiotic resistance loci, and the in the second by whole-gene sequencing. The desired outcome from both studies is to find methods to use antibiotic therapy more rationally to treat infection efficiently and effectively whilst reducing the evolution of antibiotic
resistance.
Original languageEnglish
PublisherNovo Nordisk Foundation Center for Biosustainability
Number of pages110
Publication statusPublished - 2017

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