Investigating the Effects of Genetic Background on the Fitness of Quinolone Resistance Mutations in Escherichia Coli

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Hazlett, Bryn




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.






Carleton University

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