Collateral sensitivity and the evolution of drug resistance in Escherichia coli

Recently, collateral sensitivity networks have created excitement for designing new therapies that could reduce rates of evolution of antibiotic resistance in pathogens. To explore this idea, I tested the key assumption that collateral sensitivity should reduce the frequency of mutation to resistance. Ceftazidime resistant strains showed susceptibility to chloramphenicol. It was therefore expected that growth in sub-MIC concentrations of chloramphenicol would reduce mutation rate to ceftazidime resistance, however, an increase in mutation rate was observed. There are two likely hypotheses, the first is that the increase in mutation is due to antibiotic related SOS response, and the second is that multi-drug-resistance was selected for in both cases. This highlights the need for evolutionary considerations in designing new drug therapies, as apparent patterns of collateral sensitivity may not be a sufficient criterion.

Name thesis:degree_name

Master of Science (M.Sc.)

Level thesis:degree_level

Master's

Discipline thesis:degree_discipline

Biology

Grantor dc:publisher

Carleton University

Year dc:date.issued

2017

Author dc:creator

• Deley, Trevor

Statement dc:rights

• Copyright © 2017 the author(s). Theses may be used for non-commercial research, educational, or related academic purposes only. Such uses include personal study, research, scholarship, and teaching. Theses may only be shared by linking to Carleton University Institutional Repository and no part may be used without proper attribution to the author. No part may be used for commercial purposes directly or indirectly via a for-profit platform; no adaptation or derivative works are permitted without consent from the copyright owner.

Language dc:language.iso

en

DOI

10.22215/etd/2017-11992

OAI identifier oai:identifier

oai:carleton.scholaris.ca:20.500.14718/40224