Date of Submission

Spring 2024

Academic Program

Biology

Project Advisor 1

Brooke Jude

Abstract/Artist's Statement

The escalating threat of antibiotic-resistant infections presents a formidable challenge to global health, with predictions estimating alarming mortality rates.

The misuse and overprescription of antibiotics has exerted an unprecedented selective pressure on bacterial populations, hastening the development of resistance mechanisms. Without urgent innovative action, we are shooting toward a post-antibiotic era, where common infections and minor injuries may become incurable once again. In the pursuit of a sustainable solution, a paradigm shift is imperative, with a search for non-lethal therapies that consider the broader implications of antibiotics on pathogen evolution and align with the preservation of evolutionary health.

Bacterial conjugation, a form of horizontal gene transfer (HGT), has emerged as a primary mechanism through which bacteria acquire resistance to antibiotics. The transfer of genetic material, particularly via plasmids, allows bacteria to share and disseminate antibiotic resistance genes efficiently. In this way, Conjugation contributes significantly to the spread of resistance in diverse environments. Prioritizing the discovery of targeted conjugation inhibitors (COINs) could be instrumental in combating the resistance crisis.

This study aims to understand the effects of conjugation inhibition on plasmid movement, and consequently on transfer of resistance, in E. coli. By using Crispr-Cas9 to target the TraG and TrbC genes of the RP4 plasmid in E. coli S17-1, this project aimed to reduce plasmid transfer. The TraG protein stabilizes the mating pair and links the relaxosome to the type IV secretion system (T4SS), while TrbC is crucial for pilus formation. Modifying these genes was expected to hinder conjugative transfer, thereby reducing the spread of resistance.

However, experimental challenges arose due to the E. coli S17-1 strain's unexpected antibiotic resistance profile, which invalidated the results. Despite these limitations, the study underscores the need for improved conjugation systems for future research.

Open Access Agreement

On-Campus only

Creative Commons License

Creative Commons License
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