Authors

Yueming Xu

Type

Text

Type

Dissertation

Advisor

Boon, Elizabeth M | Tonge, Peter | Schärer, Orlando | Walker, Stephen.

Date

2015-08-01

Keywords

Chemistry

Department

Department of Chemistry.

Language

en_US

Source

This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree.

Identifier

http://hdl.handle.net/11401/77169

Publisher

The Graduate School, Stony Brook University: Stony Brook, NY.

Format

application/pdf

Abstract

Nitric Oxide (NO) is a diatomic signaling molecule that regulates diverse bacterial behaviors. Its effect on cell motility has been established in many microbial systems, but the molecular mechanism remains understudied. Some bacteria have an H-NOX (Heme-Nitric oxide/OXygen-binding) domain that functions as an NO sensor. It is found in the same operon with two component signaling histidine kinases or diguanylate cyclases (DGC) that synthesize and degrade cyclic di-GMP (c-di-GMP). C-di-GMP is a secondary signaling molecule that regulates bacterial motile to sessile lifestyle transition. In this dissertation, we dedicated our effort toward understanding the effect on bacterial biofilm by NO/H-NOX regulated signaling pathway. In Vibrio harveyi, NO mediates quorum sensing (QS) through the H-NOX/HqsK pathway. We show that NO regulates flagellar production and biofilm formation in a concentration dependent manner. At low nanomolar concentration of NO, repression of flagellin coincides with enhanced biofilm. As NO concentration increases (100~200nM), a global switch takes place in protein expression and results in decreased flagellar production and less promotion of biofilm. In Shewanella woodyi, H-NOX binds a bifunctional DGC (SwHaCE). Nanomolar levels of NO repress biofilm formation through c-di-GMP degradation, and enhance phosphodiesterase activity of SwHaCE, leading to c-di-GMP hydrolysis. H-NOX regulation is not limited to iv proteins in the same operon. SwH-NOX can also interact with VhHqsK homologue, SwHK (Swoo_2833). Weaker biofilm phenotype in response to NO is attenuated when SwHK gene is disrupted in S. woodyi. In summary, NO mediates biofilm formation and protein expression via binding sensor protein H-NOX in multiple systems. Since biofilm is the predominant form of bacteria in natural aquatic environment, revealing the NO signaling mechanism would facilitate further understanding of bacterial group behavior. | 128 pages

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