Targeting the interface of riboswitches and the RNAP to develop a novel class of antibacterial – UROP Spring Symposium 2024

Targeting the interface of riboswitches and the RNAP to develop a novel class of antibacterial

Devisi Goel

Pronouns: She/Her

Research Mentor(s): Nils Walter
Research Mentor School/College/Department: Chemistry / LSA
Program:
Authors:
Session: Session 6: 3:40 pm – 4:30 pm
Poster: 50

Abstract

Antibiotics are crucial in the medical world. They allow us to fight sometimes deadly infections by killing bacteria. However, a current problem that is arising is antibiotic resistance. In 2019 it led to 1.27 million deaths from antimicrobial resistance and can cause the creation of superbugs which are incredibly dangerous [1]. Many bacteria begin to adapt and become resistant to these drugs ; the majority of clinically approved antibiotics interrupt the translation step of protein synthesis and target the ribosome [2]. However, we propose to target the interface between the RNA Polymerase (RNAP) and mRNA instead. This would be done through an antibacterial in the form of a small RNA that binds specifically to the exit channel of the RNAP and the mRNA being transcribed. Focusing on this step allows us to prevent specific genes from being transcribed which can lead to the death of the bacteria. Currently, we are looking for an RNA aptamer that will be able to bind to the RNAP exit channel. Through the use of total internal reflection fluorescence microscopy, we have been able to collect data on the following RNAP binding aptamers (RAPs); RibB, BtuB, MntP, and LysC. We are also using a hairpin and pseudoknot structured RNA to model the RNA binding to the exit channel of the RNAP. It is predicted that the MntP RAP will be most effective in creating our proposed antibacterial as our binding data has demonstrated high binding affinity to the exit channel of the polymerase, indicating its potential for disrupting the RNA transcription process. [1] Antimicrobial Resistance Collaborators. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet. 2022 Feb 12;399(10325):629-655. doi: 10.1016/S0140-6736(21)02724-0. Epub 2022 Jan 19. Erratum in: Lancet. 2022 Oct 1;400(10358):1102. PMID: 35065702; PMCID: PMC8841637. [2] Abushaheen, M. A., Muzaheed, Fatani, A. J., Alosaimi, M., Mansy, W., George, M., Acharya, S., Rathod, S., Divakar, D. D., Jhugroo, C., Vellappally, S., Khan, A. A., Shaik, J., & Jhugroo, P. (2020). Antimicrobial resistance, mechanisms and its clinical significance. Disease-a-month : DM, 66(6), 100971. https://doi.org/10.1016/j.disamonth.2020.100971

Interdisciplinary, Natural/Life Sciences

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