Abstract

Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), remains a debilitating disease that affects the health of millions annually. Understanding its ability to persist within host and resist eradication by antibiotics is of utmost importance in the effort to develop new interventions. This study will focus on the transcriptional activator WhiB7 and its regulation of the multidrug Tap efflux pump encoded by Rv1258c. WhiB7 is thought to respond to redox stress induced by antibiotics and a variety of in vivo stresses by activating multiple genes including Rv1258c. Much remains to be determined regarding the role of WhiB7 and downstream genes in Mtb virulence and drug resistance. We will create a tool for studying WhiB7-mediated gene regulation by engineering a strain of the nonpathogenic bacterium Msm expressing the mCherry fluorescent protein controlled by the Rv1258c promoter. Knocking out the native WhiB7 gene in Msm via homologous recombination will allow clear introduction of wild type and mutant versions of Mtb WhiB7. Changes in the fluorescent activity of Rv1258c promoter fusion to mCherry will indicate the effects of WhiB7 mutagenesis. Secondly, we can also use this system to confirm additional genes identified by microarray analysis that are potentially regulated by WhiB7. This will be done by cloning other promoters in front of mCherry in the Msm strain containing wild-type Mtb WhiB7. Understanding WhiB7’s role in Mycobacterium tuberculosis macrophage survival and antibiotic resistance may provide new strategies for developing drugs that can lead to a cure.

Notes

If this is your Honors thesis, and want to learn how to access it or for more information about readership statistics, contact us at STARS@ucf.edu

Thesis Completion

2014

Semester

Summer

Advisor

Rohde, Kyle; Saleh, Suha

Degree

Bachelor of Science (B.S.)

College

College of Health and Public Affairs

Department

Health Professions

Subjects

Dissertations, Academic -- Health and Public Affairs; Health and Public Affairs -- Dissertations, Academic

Format

PDF

Identifier

CFH0004654

Language

English

Access Status

Open Access

Length of Campus-only Access

5 years

Document Type

Honors in the Major Thesis

Download

Share

COinS