Date of Award
8-27-2024
Document Type
Dissertation
Degree Name
Molecular Biosciences, Ph.D.
First Advisor
Mohammad Abrar Alam
Committee Members
Asela Wijeratne, David Gilmore, Jianfeng Xu, Sudeepa Bhattacharya
Call Number
LD 251 .A566d 2024 K39
Abstract
In recent years, the rise of antibiotic-resistant bacteria has become a global concern, resulting in fewer effective antibiotics. Several conventional antibacterial agents are ineffective against these, necessitating novel molecules with enhanced efficacy and diverse actions. We developed pyrazole and thiazole-based antibacterial agents and demonstrated that they have significant potency (minimum inhibitory concentration as low as 0.39 µg/mL) against antibiotic-resistant and susceptible bacteria, as well as promising anti-biofilm and anti-persister activity. In vivo toxicity tests on Caenorhabditis elegans showed no significant harm to this model host organism at low compound concentrations. These compounds rescued C. elegans from methicillin-resistant Staphylococcus aureus (MRSA) infection and death. Investigations into the mode of action of these compounds against MRSA showed disruption of cell membrane integrity and damage to the bacterial cell wall, validated through various assays. Future research will aim to investigate their efficacy in mice and explore additional modes of action. Overall, our findings indicate the compounds' potent activity against drug-resistant bacteria, non-toxicity in a nematode model, effective rescue of nematodes from MRSA infection, cell wall and cell membrane targeting as the mode of action and show promising potential for further study in antibiotic development.
Rights Management
This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.
Recommended Citation
KC, Hansa Raj, "Antimicrobial Studies of Novel Pyrazole and Thiazole-Based Antibacterial Agents" (2024). Student Theses and Dissertations. 1084.
https://arch.astate.edu/all-etd/1084
