Date of this Version
Schacht, Andrew L.; Interplay Between the WhiB Proteins and Low Molecular Weight Thiols. University of Nebraska-Lincoln. 2018.
Mycobacterium tuberculosis (Mtb) possesses a complex regulatory system in order to respond appropriately to reduction/oxidation (redox) stresses. Included in the regulatory machinery is a family of iron-sulfur (Fe-S) cluster-containing transcription factors known as the WhiB protein family. This family of proteins have a wide diversity of downstream effects from their regulatory activities, including regulation of intracellular low-molecular weight (LMW) thiols such as mycothiol (MSH) and ergothioneine (EGT). It is currently unknown how the WhiB proteins sense and respond to redox stresses, and why some aberrant phenotypic characteristics arise in Mtb upon the loss of these proteins. The relationship of WhiB proteins to LMW thiols has not been explored, and the possibility that WhiB proteins may be regulated at the level of Fe-S cluster biosynthesis pathways has not been explored. In this thesis, I performed preliminary tests on the potential roles of LMW thiols in signaling to the WhiB proteins, including direct interaction of the thiols with the Fe-S cluster cofactors in the proteins, and the roles of LMW thiols in Fe-S cluster biosynthetic pathways. Although our preliminary data does not suggest a role of these LMW thiols in either of these systems under these experimental conditions, these experiments need to be repeated using proper controls and a more detailed analysis before conclusions can be drawn. On the other hand, further investigation into various other mechanisms of including mycothiolation of cysteines and non-disruptive ligating to the Fe-S clusters needs to be explored as well to fully understand the interplay between LMW thiols and the WhiB proteins.