Date of Award

2020

Degree Type

Dissertation

Degree Name

Doctor of Philosophy in Biological and Environmental Sciences

Specialization

Cell & Molecular Biology

Department

Cell & Molecular Biology

First Advisor

Jodi L. Camberg

Abstract

The decision for a bacterium to grow and divide may seem like a simple process, but in reality, there are many factors that influence and regulate this choice. Bacteria have been known to respond to many environmental signals or cues that represent either favorable or non-favorable growth conditions, as well as cues, secreted from other bacteria or, in the case of a pathogen, the host. It is not uncommon for bacteria that find their environment unfavorable, to alter their growth, and in some cases, even enter into a type of non-proliferative state, which we term, dormancy. Bacterial dormancy has many advantages that allow cells to survive times of hardship.

In Manuscript I, I review different strategies bacteria use to enter into and exit from dormancy, while comparing three well-studied organisms, Bacillus subtilis, Mycobacterium tuberculosis and uropathogenic Escherichia coli (UPEC). I further highlight the mechanisms in which bacteria regulate their preferred method of dormancy and specific signals or cues utilized by bacteria to stimulate their resurgence. Additionally, I discuss aspects of bacterial dormancy that may be targeted for novel therapeutics.

In Manuscript II, we further characterize UPEC dormancy. We show that quiescence is prevalent amongst clinical UPEC isolates tested, where 35% (51/145) enter into a non-proliferative state, including several isolates from the problematic multidrug-resistant pandemic lineage ST131. We report quiescent cells as being filamentous, with a population of cells containing one or more incomplete septa, implying a cell division defect. UPEC quiescence is quorum-dependent and we report, for the first time, that specific peptidoglycan fragments, serving as cues, stimulate UPEC resuscitation.

In Manuscript III, we characterize the enzymatic activity of the cell division regulator, ZapE and report the first evidence suggesting that ZapE behaves as a FtsZ polymer bundler, in vitro. We further show that ZapE is a positive regulator of UPEC quiescence and demonstrate that optimal enzymatic function of ZapE is required for the entrance into and/or maintenance of the quiescent state, as described in the Appendix.

In conclusion, this work as a whole, has furthered our knowledge pertaining to ZapE as an E. coli cell division regulator, elucidated novel cues utilized by UPEC to stimulate resuscitation out of dormancy, and, in general, has greatly advanced our understanding of bacterial quiescence and proliferation.

Available for download on Saturday, December 17, 2022

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