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Wei%2c Yahan Accepted Dissertation 11-4-16 Fa16.pdf (4.09 MB)
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Iron- and Temperature-Dependent Regulation of Shigella Dysenteriae Virulence-Associated Factors
Author Info
Wei, Yahan
Permalink:
http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1478519844517268
Abstract Details
Year and Degree
2016, Doctor of Philosophy (PhD), Ohio University, Biological Sciences (Arts and Sciences).
Abstract
Shigella
is a genus of Gram-negative pathogenic bacteria that causes shigellosis, a severe form of bacillary dysentery in human with an infectious dose of less than 100 cells. The global burden of shigellosis is estimated to be no less than 125 million infections, with the majority of both infection and resulting deaths occurring in children under the age of five. These facts, in combination with the lack of a vaccine or universally effective treatment makes understanding the molecular mechanisms underlying the pathophysiology of
Shigella
of utmost importance. To survive and successfully colonize in the host, bacterial pathogens regulate the expression of multiple virulence-associated factors in response to the changes of environmental cues. This study focused on two of the important virulence-associated processes in the infections of
S. dysenteriae
, the most virulent species in the genus of
Shigella
: 1) acquisition of essential nutritional iron via the
Shigella
heme uptake (Shu) system from the iron-limited environment within the human host, and 2) secretion of effector proteins required for the invasion processes through the type III secretion system (T3SS). Investigations presented here identify the host-associated environmental factors that regulate the expression of the specific factors required to complete the processes listed above, and characterize the molecular mechanisms underlying each regulation. Specifically, studies focused on the regulation of the Shu system demonstrate that its periplasmic binding component, ShuT, is subject to iron-dependent transcriptional regulation via the activity of the global transcriptional regulator Fur, and temperature-dependent post-transcriptionally mediated by an RNA thermometer located within the 5' untranslated region of the gene. Studies focused on the regulation of MxiG, a component of the T3SS, identify and characterize a functional RNA thermometer that mediates post-transcriptional temperature-dependent regulation. Findings in this study provide: 1) a unique example of Fur-mediated regulation via interacting with a sequence located downstream of the promoter region, and 1) the first evidence of RNA thermometer controlling expression of T3SS component. These findings could lead to revealing of further details about the molecular mechanisms of each regulatory system, and also contribute to the knowledge pool required in designing new strategies of defending against bacterial infections.
Committee
Erin Murphy (Advisor)
Jennifer Hines (Committee Chair)
Peter Coschigano (Committee Member)
Tomohiko Sugiyama (Committee Member)
Donald Holzschu (Committee Member)
Pages
169 p.
Subject Headings
Biology
;
Microbiology
Keywords
Shigella
;
virulence
;
heme uptake
;
ferric uptake regulator
;
RNA thermometer
;
type III secretion system
;
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Mendeley
Citations
Wei, Y. (2016).
Iron- and Temperature-Dependent Regulation of Shigella Dysenteriae Virulence-Associated Factors
[Doctoral dissertation, Ohio University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1478519844517268
APA Style (7th edition)
Wei, Yahan.
Iron- and Temperature-Dependent Regulation of Shigella Dysenteriae Virulence-Associated Factors.
2016. Ohio University, Doctoral dissertation.
OhioLINK Electronic Theses and Dissertations Center
, http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1478519844517268.
MLA Style (8th edition)
Wei, Yahan. "Iron- and Temperature-Dependent Regulation of Shigella Dysenteriae Virulence-Associated Factors." Doctoral dissertation, Ohio University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1478519844517268
Chicago Manual of Style (17th edition)
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Document number:
ohiou1478519844517268
Download Count:
739
Copyright Info
© 2016, all rights reserved.
This open access ETD is published by Ohio University and OhioLINK.