Investigating the Effects of Genetic Background on the Fitness of Quinolone Resistance Mutations in Escherichia Coli
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Antimicrobial resistance (AMR) is a major threat to public health. The fitness of AMR strains is determined partially by epistasis - resistance mutations may have different effects on different genetic backgrounds. I investigated the effects of genotype on the fitness of AMR in E. coli. Quinolone resistance alleles of the gyrA gene (S83L, D87N, and S83L-D87N) were transferred into a collection of knockout strains. Genetic interactions that affected fitness, both positively and negatively, were common and a variety of synthetic lethal/sick interactions were found. A number of the lethal interactors were involved in DNA repair and replication, much like gyrA itself. In subsequent validation assays, 21 of 33 strains showed a deficit in at least one fitness-related phenotype. The interactions identified here may elucidate gene functionality, and identification of synthetic lethal interactions of AMR mutations may lead to drug targets that can specifically kill resistant bacteria.
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Copyright © 2018 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.
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- 2018
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