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Chemotaxis is the biochemical and cellular process by which bacteria sense particular molecules in their environment and adjust swimming behaviors accordingly. Chemotaxis and other motility alterations in response to endogenous HOCl (hypochlorous acid, also known as bleach) are known to be necessary behaviors by which bacteria locate nutritive niches within the human body, allowing them to survive and thrive. A wide variety of gut-colonizing bacteria, including pathogens such as Escherichia coli and Salmonella. enterica depend on the Chemoreceptor Zinc-Binding (CZB) domain to sense certain aspects of their environments and alter swimming patterns accordingly. Thus, understanding the biochemistry underlying CZB signal transduction has the potential to set the foundation for future therapeutics while also expanding our understanding of the ways in which bacteria survive the often-hostile context of the human body. While existing research treated the CZB domain as a zinc sensor, my work contends that in certain molecular and cellular contexts the domain acts as an HOCl sensor instead. My work shows that the CZB possesses a highly conserved, bleach-sensitive cysteine (1/2 oxidized at 312 µM bleach) and indicates that oxidation of this cysteine results in subtle yet observable structural changes to the CZB domain. In the context of H. pylori, the CZB domain likely allows the chemoreceptor transducer-like protein D (tlpD) to swim towards sites of inflammation and injury within the stomach, thus allowing the pathogen to reach a “safe harbor” within the human stomach. This behavior illustrates the possible significance of the CZB domain in human disease: pathogens may use the domain to sense sites of inflammation, which in many cases can indicate safe and nutritive niches for these pathogens. In other contexts, CZB bleach sensing may constitute the basis for bleach chemorepulsion, where bacteria may be able to flee this generally harmful molecule. Thus, CZB bleach sensing could underly an important first step in bacterial infection and proliferation, and thus constitute a target for future therapeutic efforts. |
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