From Antimicrobial Activity to Zinc Binding: An in-depth Analysis of the Tunicate Host Defense Peptide Clavanin A
Digital Document
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http://hdl.handle.net/11134/20002:860654917
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Persons |
Persons
Creator (cre): Juliano, Samuel A. IV
Major Advisor (mja): Angeles-Boza, Alfredo
Associate Advisor (asa): Peczuh, Mark
Associate Advisor (asa): Rogue, Jessica
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Title |
Title
Title
From Antimicrobial Activity to Zinc Binding: An in-depth Analysis of the Tunicate Host Defense Peptide Clavanin A
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Origin Information
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Parent Item
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Digital Origin |
Digital Origin
born digital
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Description |
Description
Due to the overuse of conventional antibiotics, coupled with the slow rate of development of novel treatments, antibiotic resistant bacteria have been on the rise. Antimicrobial peptides (AMPs), especially those that bind to biologically relevant metal cations, present an excellent source of potential antibacterial compounds with a low incidence of resistance development. This dissertation explores one such metal binding AMP, the tunicate peptide clavanin A. In the past, clavanin A has been fairly well studied for its activity against the bacterial membrane; however, a fortuitous discovery led us to study clavanin A in the presence of metal ions. We discovered that, in the presence of Zn2+ ions, clavanin A is capable of cleaving bacterial chromosomal DNA, an activity never before reported for a zinc binding AMP. This mechanism of action also has the benefit of improving the antibacterial activity of clavanin A 16-fold. These promising results led to the exploration of AMP mechanisms of action through the application of bacterial cytological profiling. Our study represents the first use of this technique for the study of AMPs. Bacterial cytological profiling allowed us to identify that clavanin A has three distinct mechanisms of action: a membrane-based mechanism at neutral pH that is similar to that of the piscidin peptides, another membrane-based activity at low pH involving strong membrane interaction, and the zinc-based nuclease activity discussed above. The results presented in this dissertation combine to show that not only is clavanin A an interesting AMP system for study, but it is also a prime candidate for the modifications necessary to develop novel peptide-based antibiotic treatments to fend off antibiotic resistant bacteria.
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Genre
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Organizations
Degree granting institution (dgg): University of Connecticut
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Rights Statement
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Use and Reproduction |
Use and Reproduction
These materials are provided for educational and research purposes only.
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Note |
Note
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Local Identifier |
Local Identifier
OC_d_2421
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