Publication Date

2018-11-11

Availability

Embargoed

Embargo Period

2020-11-10

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PHD)

Department

Biochemistry and Molecular Biology (Medicine)

Date of Defense

2018-08-29

First Committee Member

Sylvia Daunert

Second Committee Member

Joaquin Jimenez

Third Committee Member

Sapna K. Deo

Fourth Committee Member

Alberto Caban-Martinez

Abstract

Bacterial quorum sensing (QS) is a process of communication based upon small molecules that regulates gene expression, including the genes for virulence factors and biofilm formation. QS has been implicated in playing a role in many disease states. Current advances in biotechnology have allowed for the exploitation of bacteria and their QS proteins, which has led to the development of a number of technologies, including designer analytical systems. Herein, we have employed genetically engineered bacterial whole cell biosensing systems, based on the quorum sensing regulatory proteins RhlR, LasR, and LuxR, for potential biomarker detection in physiological samples. First, we have demonstrated that the levels of acyl homoserine lactones (AHLs) in human serum can be used to indicate the presence of intestinal inflammation in Crohn’s disease (CD) patients. Specifically, in CD patients under active intestinal inflammation both short and long chain AHL levels are elevated compared to controls. Next, we have examined the levels of fecal autoinducer-2 (AI-2), employing both a mouse model for depression and a rat model for Spinal Cord Injury. In both cases, higher levels of AI-2 were correlated with disease state. In addition, we have optimized the above mentioned sensing systems for use in urine and contact lens solution matrices with promise for clinical application. Finally, based upon a previous discovery in our group that the mammalian hormone serotonin activates quorum sensing through the LasR protein and exacerbated Pseudomonas aeruginosa virulence in vitro, we developed a P. aeruginosa infection mouse model. Application of this model allowed us to determine the devastating effects of elevated serotonin during P. aeruginosa infection.

Keywords

acyl homoserine lactones; autoinducer-2; bacterial quorum sensing; inflammatory bowel disease; microbiome

Available for download on Tuesday, November 10, 2020

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