An Evaluation of Antibiotic Resistance: Structure-Activity Relationship Studies of Tetracyclic Indolines as A Novel Class of Resistance-Modifying Agents for MRSA & Analysis of Recent FDA Regulations on Antibiotic Use in Livestock
Type of Thesis
Dr. Xiang Wang
Dr. David Sherwood
Dr. Christopher Lowry
Dr. Teresa Foley
While the rate at which resistance develops against antimicrobials rises, research and development for new antimicrobials declines. By placing selective pressure on bacteria we are inadvertently forcing bacteria into expressing and propagating genes conferring high levels of resistance. Continued misuse and overuse of antibiotics, in light of the evident problem developing, must be resolved. To find a resolve, a multidisciplinary and multifaceted approach must be taken which involves 1) research and development of novel antimicrobial agents and 2) governmental regulation.
Strides in new antimicrobial drug development largely revolve around making old antibiotics usable again. Resistance-Modifying Agents (RMAs) act to re-sensitize resistant bacteria to antibiotics. Foreseeably, while these compounds have shown efficacy and certainly are of value in the present crisis, it is a short-term solution in light of the evidently rapid and dynamic capability of bacteria to respond evolutionarily. Nonetheless, a new class of RMAs, currently being researched and developed at Wang lab, hope to extend RMA lifespan through a model of synthetic compound development that targets gene expression.
Both clinically and community-acquired resistance contribute to the demolishment of a critical building block (antibiotics) of modern medicine. Arguably the most nonsensical piece of the puzzle is subtherapeutic antibiotic use in livestock, which accounts for 80% of all antibiotic use in the United States12. FDA regulations are seemingly the only feasible way to fix the problem, and yet their efforts in recent regulatory measures not only contain major loopholes, but seem altogether to be largely barren of any significant resolutions.
Cleaver, Lakota K., "An Evaluation of Antibiotic Resistance: Structure-Activity Relationship Studies of Tetracyclic Indolines as A Novel Class of Resistance-Modifying Agents for MRSA & Analysis of Recent FDA Regulations on Antibiotic Use in Livestock" (2016). Undergraduate Honors Theses. 1067.