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Leveraging Nanomaterial Design for Next Generation Antimicrobials

Stabryla, Lisa (2021) Leveraging Nanomaterial Design for Next Generation Antimicrobials. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

Silver nanoparticles (AgNPs) are promising alternatives to conventional antimicrobials due to their efficacy against a wide spectrum of bacteria. However, the mechanism of the particle contributions (distinct from their released Ag(I) ions) to microbial inactivation is not fully resolved and is needed to enable a priori design for maximizing antimicrobial activity. This dissertation demonstrates an ability to rationally design AgNPs by manipulating their morphology and establishing relationships that correlate material properties to their biological response and underlying mechanisms imparting antimicrobial activity.

A systematic literature review that critically analyzes conclusions about ion and NP contributions is conducted as an initial step to evaluate the potential impact of the particle in AgNP design. Results indicate that NP-specific effects exist and act in concert with and/or independently from solubilized Ag(I) ions, suggesting that more efficacious antimicrobials can be obtained through NP design. Next, the unintended consequence of resistance in E. coli repeatedly exposed to sublethal AgNPs concentrations is explored using an experimental evolution approach. Resistance evolves in response to AgNPs but not to Ag(I) ions alone, indicating a specific resistance to AgNPs. Selective emergence of AgNP resistance based on bacterial motility is also found, suggesting that the mechanism of resistance may be mediated by flagella. The results are promising for considering motility as a predictor of AgNP resistance and could inform design of nano-enabled antimicrobials that target non-motile bacteria. Finally, the influence of AgNP shape on antimicrobial activity is further explored as no consensus has been reached regarding the differential influence of shape on antimicrobial activity and further, the mechanism(s) underlying the differential impact. To avoid material and experimental variables confounding the resolution of shape, antimicrobial activity is evaluated with a systematically prepared and comprehensively characterized material suite of AgNP shapes with well-controlled physicochemical properties, including pseudo-spheres, cubes, and discs. Differential antimicrobial activity arises from the AgNP shapes, which is hypothesized to arise from differences in NP characteristics (e.g., surface reactivity, crystal facet).

Collectively, the research in this dissertation enables progress beyond the current disparate findings in the literature and supports the use of nanoparticle design to control antimicrobial activity and resistance outcomes.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Stabryla, Lisalms162@pitt.edulms1620000-0002-3484-1794
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairGilbertson, Leannelmg110@pitt.edulmg110
Committee MemberHaig, Sarah-Janesjhaig@pitt.edu
Committee MemberMillstone, Jilljem210@pitt.edujem210
Committee MemberStout, Janetjes20@pitt.edujes20
Date: 3 September 2021
Date Type: Publication
Defense Date: 27 May 2021
Approval Date: 3 September 2021
Submission Date: 23 July 2021
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 231
Institution: University of Pittsburgh
Schools and Programs: Swanson School of Engineering > Civil and Environmental Engineering
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: silver nanoparticles, nanotechnology, whole-genome sequencing, antimicrobial resistance, E. coli, experimental evolution, genetics
Date Deposited: 03 Sep 2021 19:00
Last Modified: 03 Sep 2021 19:00
URI: http://d-scholarship.pitt.edu/id/eprint/41488

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