This item is under embargo and not available online per the author's request. For access information, please visit http://libanswers.wustl.edu/faq/5640.

ORCID

http://orcid.org/https://orcid.org/0000-0003-4245-2868

Date of Award

Summer 8-15-2021

Author's School

Graduate School of Arts and Sciences

Author's Department

Chemistry

Degree Name

Doctor of Philosophy (PhD)

Degree Type

Dissertation

Abstract

Antibiotic resistance is on track to become the next global pandemic. As the world grapples to return to normalcy after experiencing the devastating effects of Covid-19, it is evident that a proactive approach to public health crises can mitigate the mortality rate, economic cost, and the adverse effects to the mental wellbeing of the global population. With the rapidly increasing number of multidrug resistant pathogens invading the clinical environment, the problem exists that all existing antibiotic therapies will be obsolete. The ideal solutions to this problem would be to 1) develop new antibiotics that can overcome the current resistance mechanisms, 2) create inhibitors that rescue existing antibiotics from bacterial inactivation, and 3) preemptively identify new determinants for resistance before they become a clinical hassle. The work herein elucidates the structure and mechanism of tetracycline destructases, characterizes the evolutionary landscape of these tetracycline inactivating enzymes, and discloses the design and synthesis of new inhibitors of the destructases. This comprehensive approach is designed to not only maintain the relevance of the important tetracycline drug class, but also as an effective strategy to combat the most potent form of bacterial resistance: enzymatic inactivation.

Language

English (en)

Chair and Committee

Timothy A. Wencewicz

Committee Members

John-Stephen Taylor, Meredith Jackrel, Guatam Dantas, Kevin D. Moeller,

Available for download on Wednesday, August 19, 2026

Share

COinS