Date of Award

2011

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Pharmaceutical Sciences

First Advisor

David Rowley

Abstract

Evolution has allowed bacteria to develop sophisticated methods of survival. One of these methods is biofilm production. Biofilms can be best described as complex bacterial communities embedded in a self-producing slime. Once bacteria form these biofilm communities, they become very difficult to treat with antibiotics. Along with biofilm production, another rising concern is antibiotic resistance. Bacterial resistance to many of our current antibiotics is sharply increasing, thereby creating a critical need to develop novel antimicrobial drugs.

The most successful strategy for the discovery of new antibacterial agents has been the study of molecules from nature. Most of our current clinical antibiotics derive from metabolites produced by bacteria. Antimicrobial compounds of plant origin also have enormous therapeutic potential. Previous studies have demonstrated that certain plant metabolites have potent inhibitory effects on the growth of pathogenic bacteria. Not only might metabolites from plants help mitigate infectious diseases, but they may also lack adverse side effects often associated with existing antimicrobial agents, including hypersensitivity, allergic reaction, and immunosuppression. Therefore, future efforts to discover new antimicrobial drugs should also include the evaluation of new natural products from both microbes and plants.

In this thesis, Chapter 1 describes an investigation to classify and quantify biofilm production in unique clinical strains of methicillin-resistant Staphylococcus aureus (MRSA). Staphylococcus aureus bacteria are responsible for causing a wide range of diseases and many are capable of biofilm production. To date, the largest focus of biofilm research has been on S. epidermidis and Pseudomonas aeruginosa. Few investigators have addressed the basic and central question: “What percentage of our clinical S. aureus bacteria produce biofilms and from what patient source are they most likely identified?” Two hundred and nineteen (n = 219) clinical methicillin-resistant S. aureus (MRSA) isolates obtained from patients at the Veterans Affairs Medical Center (VAMC) in Providence, Rhode Island were evaluated. I evaluated biofilm formation using a modified microtiter-plate assay, and used a statistical approach to quantifying biofilm production. The results indicate that biofilm production is most frequently encountered in clinical MRSA from catheter sources. The surface area of these catheters may provide the ideal conditions for biofilm growth, especially in urine. Interestingly, a lesser incidence of biofilm production was observed by MRSA isolates obtained in the nares.

Chapter 2 describes a phytochemical investigation of plant metabolites from Hypericum species that inhibit bacterial growth as well as biofilm production in Gram-positive bacteria. For this study, seven acylphloroglucinol metabolites were obtained from Dr. Geneive Henry at Susquehanna University. I tested each compound in assays that measure both bacterial growth and biofilm production. The results showed that not only do some of these metabolites inhibit bacterial growth, but they also inhibit biofilm growth at sub-MIC concentrations. Important findings from this investigation included new structure-activity relationships demonstrating the importance of certain functional groups to the antibacterial nature of these metabolites. These results suggest that Hypericum spp. deserve further attention as a source of new antimicrobial agents.

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