Date of Award
2026-05-01
Degree Name
Doctor of Philosophy
Department
Chemistry
Advisor(s)
Eda Koculi
Abstract
The objective of this work is to decipher fundamental protein-RNA processes that are crucial for bacterial survival and viral replication. Ribosomes are protein-RNA complexes essential for bacterial viability, and actively translating ribosomes are targeted by approximately 60% of currently used antibiotics. Recently, ribosome biogenesis has also emerged as a potential antibiotic target. High-resolution mass spectrometry experiments demonstrate that proteins involved in Escherichia coli (E.coli) ribosome biogenesis and antibiotic response are differentially regulated during the stationary and exponential growth phases. This is observed both in cells that possess and in those that lack the RNA helicase DbpA. DbpA mediates structural rearrangements in the peptidyl transferase center of the ribosome, a region essential for its function. Transcriptomic analysis using Illumina Next Generation Sequencing reveals that E.coli cells lacking YihF, a protein of unknown function, reprogram multiple cellular processes, including ribosome biogenesis. In addition, the malachite green assay was optimized for high-throughput screening of Zika virus RNA-dependent RNA polymerase (RdRp). This enzyme is essential for Zika virus propagation and replication and has no similarity to human polymerases, making it an ideal target for antiviral drug development. Employing the optimized malachite green assay, 204 compounds from the Natural Product Set IV of the National Cancer Institute Developmental Therapeutics Program were screened. Two compounds, purpurogallin and digallic acid, were identified as modulators of Zika virus RdRp activity. Combined, this work reveals novel ribosome biogenesis processes, uncovers phase-specific bacterial targets for new antibiotics, and identifies two promising small-molecule inhibitors of Zika virus RdRp. Thus, establishing a strong foundation for future antimicrobial and antiviral drug development.
Language
en
Provenance
Received from ProQuest
Copyright Date
2026-05
File Size
288 p.
File Format
application/pdf
Rights Holder
Vanessa Beatriz Aitken Silva
Recommended Citation
Aitken Silva, Vanessa Beatriz, "Rna-Centered Molecular Machines In Infection And Cellular Growth: Zika Polymerase Inhibition And Bacterial Ribosome Biogenesis" (2026). Open Access Theses & Dissertations. 4616.
https://scholarworks.utep.edu/open_etd/4616