Plasmid Instability: Measurement and Use in Antimicrobial Action

Crewe, Nicola (2004) Plasmid Instability: Measurement and Use in Antimicrobial Action. PhD thesis, University of Hertfordshire.

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Abstract

The discovery of antibiotics in the early 20th century revolutionised medicine, but quickly bacteria began to demonstrate resistance to these agents. Antibiotic resistance is still on the increase, and soon, if this trend continues, bacterial infections may not be treatable with antibiotics. In an effort to prevent this occurring, the search for novel antibiotics is under way and new antibiotic targets are being considered. One target that has not been studied in depth is the partitioning systems of bacterial plasmids. Disruption of plasmid partition would prevent effective plasmid inheritance, which, in the case of resistance plasmids, would render the host cell antibiotic sensitive.

The aim of this study was to determine whether plasmid partitioning is a viable target for a new antibiotic. A series of plasmids that contained genetically altered partitioning systems was used, which provided a range of plasmid stabilities. The plasmids all conferred antibiotic resistance on the host cell, allowing the effect of plasmid instability on a population grown in the presence of antibiotics to be determined.

Several different methods of cell culture were used. Simple batch culture experiments allowed the observation that few plasmid-free cells were produced from cells containing plasmids that had a functional system. In contrast, plasmids containing a faulty system were found to be rapidly lost from the host cells. Steady-state chemostat culture was used to provide a simple model of a clinical infection. The formation of equilibria between plasmid-free and plasmid-bearing cells was observed, and the cultures contained a large proportion of plasmid-free cells when the experiments involved unstable plasmids. The slow growth rate of cultures in the chemostat was seen to dramatically affect the inheritance of plasmids relying on random distribution.

Finally, cultures were subjected to washout in order to determine their maximum specific growth rate (µmax). While the results from these experiments are not entirely conclusive, there is a strong indication that the growth rate of cultures containing unstable plasmids grown in the presence of antibiotics is reduced.

Keywords:Plasmid, Antibiotic resistance, Partition systems, Chemostat culture
Subjects:C Biological Sciences > C500 Microbiology
Divisions:College of Science > National Centre for Food Manufacturing
ID Code:34490
Deposited On:11 Dec 2018 21:20

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