Graduation Date

Spring 5-5-2018

Document Type

Thesis

Degree Name

Master of Science (MS)

Programs

Pathology & Microbiology

First Advisor

Marilynn A. Larson, PhD

Second Advisor

Steven H. Hinrichs, MD

Third Advisor

Paul D. Fey, PhD

Abstract

Francisella tularensis is the causative agent of the disease tularemia and a select agent. The genome of this pathogen contains many insertion sequence (IS) elements with ISFtu1 being the most abundant. ISFtu1 expression and the contribution of this IS element to differential gene expression in the F. tularensis subpopulations was evaluated. Full-length and truncated ISFtu1 sense and antisense transcriptional expression was detected. The prototype A.I strain (Schu S4) had considerably higher expression levels of ISFtu1 and the adjacent genes than the wild type A.I strain (NE061598). The A.II strains (WY96-3418 and WY-00W4114) had similar expression levels for ISFtu1 and the adjacent genes. In the highly virulent A.I strains, a bicistronic transcript encoding the universal stress protein (Usp) and a downstream ISFtu1 was highly expressed during early and mid log growth phase when provisions were plentiful, and was induced 2-fold by nitric oxide and a polyamine. During late log growth and stationary phase, only monocistronic transcripts for usp and ISFtu1 were being moderately expressed. Intrinsic transcription termination sequences were not apparent between usp and ISFtu1. Secondary RNA structure models indicated that the bicistronic transcript will form more readily than the monocistronic usp transcript. The co-expression of ISFtu1 and the adjacent gene(s) may provide a fitness advantage by regulating expression and/or transcript stability of the co-transcribed gene(s). Additional study will provide a better understanding of the contribution of IS elements to the differential gene expression and virulence observed for the various F. tularensis clades.

Available for download on Sunday, April 26, 2020

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