07/11/2023
By Kwok Fan Chow
The Kennedy College of Science, Department of Chemistry, invites you to attend a Ph.D. Dissertation defense by Hasitha Netolpitiya Gamage entitled “Antivirulence and Metal-based Approaches to Antimicrobial Action.”
Degree: Doctoral
Location: Shah Hall, Room 305
Date: Friday, July 28, 2023
Time: 1 p.m.
Committee Chair: Prof. Olof Ramstrom, Department of Chemistry, University of Massachusetts Lowell
Committee Members:
- Prof. Marina Ruths, Department of Chemistry, University of Massachusetts Lowell
- Prof. Matthew Gage, Department of Chemistry, University of Massachusetts Lowell
- Prof. Zhaohui Zhou, Department of Chemistry and Chemical Biology, Northeastern University
Abstract:
Pathogens are evolving toward multidrug resistance at a significant pace rendering the current antibiotics obsolete. These pathogens can produce virulence factors (VFs) that facilitate their pathogenicity. Targeting these virulence factors VFs to attenuate pathogen proliferation has been a widely explored avenue. Pseudomonas aeruginosa is a major nosocomial pathogen that produces several VFs, including the iron-scavenging molecules known as siderophores and secretory proteases. While all genes involved in VF metabolism are tightly regulated, the pseudomonal siderophore pyochelin metabolic genes are partially regulated by PchR. Part of this study synthesized pyochelin analogs to carry antimicrobial cations such as GaIII and InIII into the pseudomonal cells, including multidrug-resistant isolates. Another part of our study developed a metallophore-responsive dynamic drug carrier. The efficacy of these partly chitosan-based drug carriers on Gram-positive, Gram-negative, and pseudomonal multidrug-resistant pathogens have been evaluated. In addition, gold nanoclusters that are analogs of the FDA-approved drug Auranofin have been synthesized and assessed as antimicrobials against several pathogens. Their significantly potent activity enhancement upon the addition of thiourea elevated them as a broad-spectrum antimicrobial. These studies evaluated the efficacy of the therapeutics described above toward biofilm eradication and assessed their cytotoxicity on mammalian cells. Another drug carrier sensitive to pseudomonal virulence protease LasA has been developed using polycationic chitosan and a LasA-sensitive peptide as the crosslinker. As it is vital to develop novel antimicrobials and targeted drug carriers to overcome antimicrobial resistance, our studies have identified potential candidates that can be further developed as antimicrobials for clinical settings.
All interested students and faculty members are invited to attend.