Date Approved

6-26-2020

Embargo Period

6-29-2020

Document Type

Thesis

Degree Name

M.S. Pharmaceutical Sciences

Department

Chemistry and Biochemistry

College

College of Science & Mathematics

First Advisor

Perez, Lark

Second Advisor

Caputo, Gregory

Third Advisor

Jonnalagadda, Subash

Subject(s)

Drug resistance in microorganisms; Bacteria

Disciplines

Medicinal and Pharmaceutical Chemistry | Pharmacy and Pharmaceutical Sciences

Abstract

Widespread usage of antibiotics is a growing concern due to antibiotic resistance development in bacteria. This is due to common use of antibiotics in agricultural, livestock, and clinical usage. Antibiotic resistance is developing at a rate in which it is outpacing new drugs on the market. New strategies in drug development are necessary to combat the increasing resistance. We designed several motifs of sugar-modified nanoparticles to inhibit the biofilm formation of Pseudomonas aeruginosa.

P. aeruginosa is an opportunistic pathogenic bacterium that is responsible for common life-threatening infection in hospitals. This gram-negative opportunistic pathogenic bacterium infects hosts with compromised immune systems and contributes to complications in patients suffering from pneumonia, cystic fibrosis, and other immune compromising conditions. Biofilm formation from P. aeruginosa is used as an attack mechanism and adds to antibiotic resistance. Regulation of biofilms are performed by quorum sensing.

P. aeruginosa lectins, LecA and LecB, are two sugar-binding proteins distinct in structure, binding preference and involvement of biofilm formation in this pathogen. Lectins, LecA and LecB, are specific to D-Galactose, and L-Fucose, respectively. Modifying the surface of our NP with the lectin-specific sugars achieves lectin binding selectivity, where nanoparticles are specific only to the targeted lectin. Modifying the surface of nanoparticles with these specific sugars provides a unique opportunity to not only bind selectively to P. aeruginosa, but also inhibit biofilm formation by disrupting colonization of the bacterium. Nanoparticles may also allow for antibiotic encapsulation, which could lead to pathogen specific use of antibiotics.

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