The evolutionary ecology of antibiotic resistance and antibiotic resistance plasmids in Escherichia coli

Frances Medaney

Research output: ThesisDoctoral Thesis

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Antibiotic resistance is ‘as big a risk as terrorism’ according to H.M. Government Chief Medical Officer in March 2013. New insights into the ecology and evolution of resistance are, therefore, a research priority if we are to avert this crisis. Antibiotic resistance genes are often carried on plasmids, mobile genetic elements that allow rapid dissemination of resistance through bacterial populations. However, little is known about the ecology of plasmids and associated antibiotic resistance in natural bacterial communities. In addition, detoxifying antibiotic resistance is often cited as a social trait in bacteria. This is of particular interest because many virulence associated traits, including siderophore production and toxin secretion, are cooperative. This thesis examines the evolutionary ecology of both antibiotic resistance and resistance plasmids in E.coli in four related studies: i) an examination cooperative β lactam resistance using laboratory competition experiments, which demonstrated that cooperative resistance occurs only under very specific conditions: the presence of ‘persister’ susceptible colonies, which are not resistant, but can tolerate high concentrations of antibiotic in the presence of resistant cells; ii) sequencing of non-resistance plasmids, which demonstrated the wide variety of plasmids present in one bacterial community, and highlighted our limited understanding of plasmid gene function; iii) a population study of E.coli and its plasmids which found surprisingly low levels of antibiotic resistance, and interesting patterns of plasmid-host diversity and population structuring; and iv) laboratory plasmid maintenance experiments which found a complex, frequency-dependent pattern governing plasmid persistence. These results bring into question current assumptions about resistance as a cooperative trait, and suggest that frequency-dependence could be key to explaining plasmid maintenance dynamics. They also provide insights into natural plasmid populations through sequencing and field study, which contribute to our understanding of the spread of antibiotic resistance genes.
Original languageEnglish
Awarding Institution
  • Royal Holloway, University of London
  • Raymond, Benjamin, Supervisor
  • Ellis, Richard J., Supervisor, External person
Thesis sponsors
Award date1 Feb 2015
Publication statusUnpublished - 2015


  • antibiotic resistance
  • antibiotics
  • Plasmids
  • Bacteria
  • social evolution
  • Escherichia coli
  • plasmid ecology

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