Exploration of novel small-molecule signaling pathways in Staphylococcus aureus.

Exploration of novel small-molecule signaling pathways in Staphylococcus aureus.

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Bibliographic Details
Author / Creator:	Ji, Quanjiang.
Imprint:	2014.
Description:	218 p.
Language:	English
Format:	E-Resource Dissertations
Local Note:	School code: 0330.
URL for this record:	http://pi.lib.uchicago.edu/1001/cat/bib/10168868

Hidden Bibliographic Details
Other authors / contributors:	University of Chicago.
ISBN:	9781321224016
Notes:	Advisor: Chuan He. Thesis (Ph.D.)--The University of Chicago, Division of the Physical Sciences, Department of Chemistry, 2014. Dissertation Abstracts International, Volume: 76-02(E), Section: B.
Summary:	Small-molecule signaling is one of the most crucial cellular processes utilized by biological systems to adapt to changing environment and stimulus. In particular, Staphylococcus aureus has developed various kinds of signaling pathways to sense host and antibiotic stress for successful infection and antibiotic resistance development. In this thesis, we have explored three novel virulence and antibiotic resistance related small-molecule signaling pathways: 1) we discovered a novel quinone signaling pathway mediated by a quinone sensing and response regulator QsrR.We also illustrated the detailed quinone sensing mechanism through structural study of QsrR-DNA and QsrR-quinone complexes; 2) we explored a novel iron-sulfur containing two-component system AirSR which is further discovered to be a master of reactive oxygen species (ROS) sensor; 3) we studied the ROS sensing mechanism of a master regulator of cysteine metabolism CymR. The key cysteine residue Cys25 in CymR can be oxidized by ROS and may further react with cellular free thiols to form mixed disulfide bond to cause the conformational change of CymR. The study of these novel small-molecule signaling pathways may pave the way for rational design of small molecule inhibitors to counter infection.