Magnetic Extraction of Acinetobacter baumannii Using Colistin

Jul 11, 2017 - This result demonstrates the potential for implementation of this technology into micro- or mesofluidic-based separation environments t...
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Magnetic Extraction of Acinetobacter baumannii using Colistin Functionalized #-FeO/Au Core/Shell Composite Nanoclusters 2

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Charleson S Bell, Raquel Mejias, Sinead Miller, Jasmine Greer, Mark McClain, Timothy L. Cover, and Todd D. Giorgio ACS Appl. Mater. Interfaces, Just Accepted Manuscript • DOI: 10.1021/acsami.7b07304 • Publication Date (Web): 11 Jul 2017 Downloaded from http://pubs.acs.org on July 12, 2017

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ACS Applied Materials & Interfaces

Magnetic Extraction of Acinetobacter baumannii using Colistin Functionalized γ-Fe2O3/Au Core/Shell Composite Nanoclusters Charleson S. Bell, Ph.D.1, Raquel Mejías, Ph.D.1, Sinead E. Miller, Ph.D.1, Jasmine M. Greer1, Mark S. McClain, Ph.D.2, Timothy L. Cover, M.D2,3, Todd D. Giorgio1,*, Ph.D. 1

Department of Biomedical Engineering, Vanderbilt University, VU Station B 351631, Nashville, TN 37235-1631, USA

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Vanderbilt University Medical Center, Department of Medicine, Division of Infectious Disease, Vanderbilt University School of Medicine, Nashville, TN 37232, USA 3

Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN 37212, USA

* Corresponding author. Tel.: +1 615 322 3756; fax: +1 615 343 7919 E-mail address: [email protected]

ABSTRACT Keywords: Magnetic nanoclusters, iron oxide, gold, bacteria capture, colistin, magnetic separation

Acinetobacter baumannii is a gram-negative bacterium of increasing concern due to its virulence and persistence in combat and healthcare environments. The incidence of both community-acquired and nosocomial A. baumannii infections is on the rise in foreign and domestic healthcare facilities. Treatment options are limited due to the acquisition of multi-drug resistance to the few effective antibiotics. Currently, the most effective pharmaceutically-based treatment for multi-drug-resistant A. baumannii infections is the antibiotic colistin (polymyxin E). To minimize side effects associated with administration of colistin or other toxic antimicrobial agents, we propose the development of a nanotechnology-mediated treatment strategy. In this design-based effort, colistin functionalized multilayered, inorganic, magnetoplasmonic nanoconstructs were fabricated to bind to the surface of A. baumannii. This result, for the first time, demonstrates a robust, pharmaceutical-based motif for high affinity, composite nanoparticulates targeting the A. baumannii surface. The antibiotic-activated nanomaterials demonstrated 1

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cytocompatibility with human cells, and no acute bacterial toxicity at nanoparticle to bacterial concentrations