DOI
https://doi.org/10.25772/SAW4-4H12
Author ORCID Identifier
https://orcid.org/0000-0002-5548-2831
Defense Date
2020
Document Type
Dissertation
Degree Name
Doctor of Philosophy
Department
Microbiology & Immunology
First Advisor
Dr. Dennis Ohman
Second Advisor
Dr. Todd Kitten
Third Advisor
Dr. Phillip Hylemon
Fourth Advisor
Dr. Rebecca Martin
Fifth Advisor
Dr. Richard Marconi
Abstract
Pseudomonas aeruginosa is a Gram-negative bacterium found in various environmental niches including soil, water, hospital environments, and within a broad range of hosts. It is well known for its metabolic versatility and intrinsic and acquired resistance to a variety of antimicrobial agents. Moreover, this bacterium has a remarkable ability to adapt and survive in suboptimal environments by altering its transcriptional profile in response to nutrient deprivation, changes in temperature and pH, osmotic stress, the presence of reactive oxygen species (ROS), and exposure to antibiotics and host defenses. P. aeruginosa colonizes individuals with compromised immune systems and severe burn injuries and is a leading cause of hospital-acquired infections due to the contamination of urinary catheters, surgical implants, and respiratory ventilators with bacterial biofilms. This opportunistic pathogen is particularly dangerous to individuals with impaired mucociliary clearance like patients with cystic fibrosis (CF) or chronic obstructive pulmonary disease (COPD) where an acute infection of the lungs usually progresses to chronic pulmonary disease. In the last decade, non-coding small RNAs (sRNAs) have been recognized as diverse regulators of gene expression, acting at the post-transcriptional level as modulators of mRNA translation and stability and often interacting with the translational machinery of sigma factors in response to environmental signals. The advent of RNA-sequencing (RNA-seq) technology and the advancements made since its conception have proven invaluable in the identification of hundreds of novel sRNAs in diverse bacteria, providing valuable insights into complex regulatory networks of pathogenic microorganisms. Exposure to stressful environmental conditions such as those found in the cystic fibrosis (CF) lung results in a fundamental transition in the gene expression profile of P. aeruginosa directed by the alternative sigma factor, σ22 and a subsequent shift to a recalcitrant, chronic infection that is the primary cause of morbidity and mortality in these patients. Regulatory sRNAs are likely to have a profound impact on these stress-induced transitions and potentially control a substantial degree of regulatory network reprogramming. Understanding these complex regulatory networks will offer valuable insight into the obscure pathophysiology of Pseudomonas aeruginosa during chronic lung infections.
Rights
© Christine M. Van Duyn 2020 All Rights Reserved
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
12-2-2020