University of Illinois at Chicago
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Elucidating Molecular Mechanisms Involved in Rgg-SHP Transcription Regulation During Streptococcal quoru

thesis
posted on 2022-05-01, 00:00 authored by Kaitlyn M Tylor
Rgg proteins are a class of peptide pheromone-binding transcriptional regulators found in the cytoplasm of most genera of the bacterial phylum Firmicutes. In Group A Streptococcus (GAS), Rgg2 and Rgg3 proteins regulate the transcription of genes involved in moderating group behaviors such as biofilm formation, lysozyme resistance, cell aggregation, and immunosuppression1, in a process known as quorum sensing (QS). A short hydrophobic peptide (SHP) induces QS-related genes by altering the function of the individual Rgg transcriptional regulators. Interestingly, Rgg2 and Rgg3, though highly similar proteins, display opposing activities in transcription regulation; Rgg2 is an activator, whereas Rgg3 is a repressor. We are characterizing the properties of these Rgg proteins, including peptide binding, DNA binding, interactions with RNA polymerase, and oligomerization. The goal is to characterize how these SHP-responsive proteins undergo allosteric conformational shifts resulting in positive recruitment and/or interaction with RNA polymerase holoenzyme. Using biochemical and genetic approaches, we found that SHP induces a conformational shift in Rgg proteins resulting in productive interactions with RNA polymerase holoenzyme and initiation of transcription. Understanding how Rgg proteins initiate or block transcription, and how their activity changes when bound to the SHP pheromones, will advance our understanding of QS in GAS and other pathogenic members of the phylum Firmicutes. Characterization of Rgg-SHP systems expands our efforts to interfere with QS and therefore manipulate bacterial behavior for therapeutic purposes.

History

Advisor

Federle, Michael

Chair

Federle, Michael

Department

Microbiology & Immunology

Degree Grantor

University of Illinois at Chicago

Degree Level

  • Doctoral

Degree name

PhD, Doctor of Philosophy

Committee Member

McLachlan, Alan Freitag, Nancy Behnsen, Judith Vasquez-Laslop, Nora Mankin, Alexander

Submitted date

May 2022

Thesis type

application/pdf

Language

  • en

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