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Exploiting the toolbox of directed evolution to combat the antimicrobial resistance pandemic

Steenbeek, Koen Jan van (2021) Exploiting the toolbox of directed evolution to combat the antimicrobial resistance pandemic. Bachelor's Thesis, Biology.

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Abstract

In this review it was explored how the concept of directed evolution can be used to combat the antimicrobial resistance crisis with special focus on antifungals. Directed evolution is the targeted artificial evolution of a specific DNA segment. In vitro mutagenesis techniques have been the most dominant method of generating mutant libraries and evolving antimicrobials. They are easily applicable, but do have certain disadvantages such as being labor and time intensive, limited size of target DNA that can be mutagenized and some methods are biased towards certain mutations. In vivo mutagenesis methods are conceptually more difficult, but solve most of the issues in vitro mutagenesis has. Even though its large potential, empirical evidence of antimicrobials evolved using in vivonmutagenesis is still minimal. As of now, the screening step is the bottleneck and determines throughput. A phage based evolution method is fully continuous eliminating intermediary screening steps and thus increasing throughput. A screening method of an experimental evolution set-up might also allow for continuous screening and increased throughput. Directed evolution can also be used to resensitize resistant pathogens to certain antimicrobials and to increase the lifetime of current and future drugs. Lastly, directed evolution methods have also been developed to mapp (genomic) resistance profiles and fitness landscapes of antimicrobials.

Item Type: Thesis (Bachelor's Thesis)
Supervisor name: Billerbeck, S.K.
Degree programme: Biology
Thesis type: Bachelor's Thesis
Language: English
Date Deposited: 28 May 2021 12:30
Last Modified: 28 May 2021 12:30
URI: https://fse.studenttheses.ub.rug.nl/id/eprint/24460

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