Author ORCID Identifier

https://orcid.org/0000-0002-7423-3806

Year of Publication

2020

Degree Name

Master of Science (MS)

Document Type

Master's Thesis

College

Agriculture, Food and Environment

Department

Veterinary Science

First Advisor

Dr. Carrie L. Shaffer

Second Advisor

Dr. David W. Horohov

Abstract

Rhodococcus equi is a significant cause of pneumonia in foals and immunocompromised humans. Antimicrobial resistance among R. equi isolates has developed as a consequence of inappropriate stewardship and bacterial evolution, leading to an increased rate of treatment failures that typically result in foal fatality. In the current study, we evaluated the efficacy of antimicrobial silver nanoparticle (AgNP) complexes in controlling R. equi growth. Previous studies characterizing AgNP-induced antibacterial effects in other Gram-positive pathogens led us to hypothesize that silver nanoparticle antimicrobials impact R. equi viability and intracellular replication. We therefore investigated the effect of silver nanoparticle complexes on R. equi growth; assessed whether silver nanoparticle complexes prevent intracellular replication of R. equi; and evaluated the safety of silver nanoparticles in host cells. The results presented here demonstrate that silver nanoparticle complexes exhibit bactericidal activity against R. equi. However, AgNP effective concentrations also induced rapid apoptosis and secondary necrosis of macrophage-like cells and equine pulmonary endothelial cells, suggesting multiple mechanisms of cytotoxicity. Overall, this study demonstrates that while silver nanoparticle-based therapeutics can effectively control R. equi proliferation, application of AgNP complexes as a treatment strategy for controlling rhodococcal disease may be limited by adverse host cellular effects.

Digital Object Identifier (DOI)

https://doi.org/10.13023/etd.2020.051

Funding Information

This work was supported by the USDA National Institute of Food and Agriculture, HATCH project 1015612, received 2017.

This work was supported by the Paul Mellon Fellowship Departmental Fund through the Maxwell H. Gluck Equine Research Center at the University of Kentucky, received 2017.

Available for download on Tuesday, August 11, 2020

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