A Cationic Zn-Containing Porphyrin Exhibits Potent Antibiotic Activity Against Cells and Biofilms of the ESKAPE Pathogen Pseudomonas aeruginosa: A Mechanistic Study

Date of Award

2021

Degree Name

Ph.D. in Biology

Department

Department of Biology

Advisor/Chair

Jayne Robinson

Abstract

Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen that has the ability to survive in both aerobic and anaerobic environments and on abiotic and biotic surfaces. Resistance to most of the current antimicrobials has enabled this bacterium to be included in the ESKAPE pathogens list. Further, formation of biofilms prevents entry of antimicrobials into the matrix, thereby making them 1000x more resistant than planktonic cells. The need for new antimicrobials that are effective against both planktonic and biofilm-associated cells, led us to explore the antibacterial activity of porphyrins. Ultimately, we focused on a novel zinc II porphyrin (ZnPor), a product of this research, due to its powerful antibacterial properties against P. aeruginosa (PAO1 strain). Chapter 1 compiles and summarizes current issues of antibiotic resistance, use of porphyrins as an antimicrobial via PDT, advantages and disadvantages of PDT, model organism and its multidrug resistance. Following this review, Chapter 2 unravels the effect of ZnPor on planktonic and biofilm cells and provides evidence for the target and mechanism of action of this porphyrin. iv We show ZnPor enhances the effectiveness of currently used antibiotics that, by themselves, are not effective against the biofilms of PsA. Combination therapies have advantages in that they reduce toxic or undesirable side effects. In Chapter 3, the interaction of ZnPor and the chromosomal DNA from Pseudomonas aeruginosa.is studied using Circular Dichroism. The Comparative study using circular dichroism explains the consequential change in secondary structure of PAO1 DNA due to porphyrin-DNA interaction. Finally, Chapter 4 summarizes the overall research and provides future directions.

Keywords

Biology, Microbiology

Rights Statement

Copyright © 2021, author.

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