Graduation Year

2021

Document Type

Dissertation

Degree

Ph.D.

Degree Name

Doctor of Philosophy (Ph.D.)

Degree Granting Department

Biology (Cell Biology, Microbiology, Molecular Biology)

Major Professor

Lindsey Shaw, Ph.D.

Committee Member

Prahathees Eswara, Ph.D.

Committee Member

Xingmin Sun, Ph.D.

Committee Member

Burt Anderson, Ph.D.

Keywords

Acinetobacter baumannii, Biofilm, Gene Regulation, ncRNA, Pathogenesis, Staphylococcus aureus

Abstract

Staphylococcus aureus and Acinetobacter baumannii are two highly successful human pathogens, which have adopted very different, but effective survival strategies. The success of S. aureus is attributed to the tight regulation of an arsenal of virulence factors. Conversely, A. baumannii lacks what would be considered traditional virulence factors and, instead, has developed a high tolerance for environmental stress, which allows it to persist in unforgiving environments, including nosocomial settings and the human body. One common characteristic of these two organisms is their proclivity for biofilm formation. Herein, we discuss the diverse mechanisms governing biofilm formation for A. baumannii and S. aureus. We describe the core regulatory elements driving attachment, proliferation, maturation, and dissemination of the S. aureus biofilm, and dive into the distinct regulation of biofilms amongst S. aureus strains that may reflect their propensity to cause particular types of infection. We also define the role of the non-coding RNA, SSR42, as it pertains to biofilm formation, and show that despite being highly conserved, the role of this regulatory RNA is quite divergent. Comparatively, much less is known about A. baumannii biofilm regulation. To this end, this work has investigated the global transcriptomic regulation within A. baumannii biofilm and successfully identified 24 novel biofilm regulators. Accordingly, we have characterized the role of one such factor, cold shock protein C, as a putative RNA chaperone that impacts A. baumannii antimicrobial susceptibility and virulence. Collectively, this work furthers our understanding of the divergent mechanisms governing bacterial biofilm formation.

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