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Synergistic Photothermal and Antibiotic Killing of Biofilm-Associated Staphylococcus aureus Using Targeted Antibiotic-Loaded Gold Nanoconstructs

[Image: see text] Resistance to conventional antibiotics is a growing public health concern that is quickly outpacing the development of new antibiotics. This has led the Infectious Diseases Society of America (IDSA) to designate Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Ac...

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Autores principales: Meeker, Daniel G., Jenkins, Samir V., Miller, Emily K., Beenken, Karen E., Loughran, Allister J., Powless, Amy, Muldoon, Timothy J., Galanzha, Ekaterina I., Zharov, Vladimir P., Smeltzer, Mark S., Chen, Jingyi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2016
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4945994/
https://www.ncbi.nlm.nih.gov/pubmed/27441208
http://dx.doi.org/10.1021/acsinfecdis.5b00117
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author Meeker, Daniel G.
Jenkins, Samir V.
Miller, Emily K.
Beenken, Karen E.
Loughran, Allister J.
Powless, Amy
Muldoon, Timothy J.
Galanzha, Ekaterina I.
Zharov, Vladimir P.
Smeltzer, Mark S.
Chen, Jingyi
author_facet Meeker, Daniel G.
Jenkins, Samir V.
Miller, Emily K.
Beenken, Karen E.
Loughran, Allister J.
Powless, Amy
Muldoon, Timothy J.
Galanzha, Ekaterina I.
Zharov, Vladimir P.
Smeltzer, Mark S.
Chen, Jingyi
author_sort Meeker, Daniel G.
collection PubMed
description [Image: see text] Resistance to conventional antibiotics is a growing public health concern that is quickly outpacing the development of new antibiotics. This has led the Infectious Diseases Society of America (IDSA) to designate Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species as “ESKAPE pathogens” on the basis of the rapidly decreasing availability of useful antibiotics. This emphasizes the urgent need for alternative therapeutic strategies to combat infections caused by these and other bacterial pathogens. In this study, we used Staphylococcus aureus (S. aureus) as a proof-of-principle ESKAPE pathogen to demonstrate that an appropriate antibiotic (daptomycin) can be incorporated into polydopamine-coated gold nanocages (AuNC@PDA) and that daptomycin-loaded AuNC@PDA can be conjugated to antibodies targeting a species-specific surface protein (staphylococcal protein A; Spa) as a means of achieving selective delivery of the nanoconstructs directly to the bacterial cell surface. Targeting specificity was confirmed by demonstrating a lack of binding to mammalian cells, reduced photothermal and antibiotic killing of the Spa-negative species Staphylococcus epidermidis, and reduced killing of S. aureus in the presence of unconjugated anti-Spa antibodies. We demonstrate that laser irradiation at levels within the current safety standard for use in humans can be used to achieve both a lethal photothermal effect and controlled release of the antibiotic, thus resulting in a degree of therapeutic synergy capable of eradicating viable S. aureus cells. The system was validated using planktonic bacterial cultures of both methicillin-sensitive and methicillin-resistant S. aureus strains and subsequently shown to be effective in the context of an established biofilm, thus indicating that this approach could be used to facilitate the effective treatment of intrinsically resistant biofilm infections.
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spelling pubmed-49459942016-07-18 Synergistic Photothermal and Antibiotic Killing of Biofilm-Associated Staphylococcus aureus Using Targeted Antibiotic-Loaded Gold Nanoconstructs Meeker, Daniel G. Jenkins, Samir V. Miller, Emily K. Beenken, Karen E. Loughran, Allister J. Powless, Amy Muldoon, Timothy J. Galanzha, Ekaterina I. Zharov, Vladimir P. Smeltzer, Mark S. Chen, Jingyi ACS Infect Dis [Image: see text] Resistance to conventional antibiotics is a growing public health concern that is quickly outpacing the development of new antibiotics. This has led the Infectious Diseases Society of America (IDSA) to designate Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species as “ESKAPE pathogens” on the basis of the rapidly decreasing availability of useful antibiotics. This emphasizes the urgent need for alternative therapeutic strategies to combat infections caused by these and other bacterial pathogens. In this study, we used Staphylococcus aureus (S. aureus) as a proof-of-principle ESKAPE pathogen to demonstrate that an appropriate antibiotic (daptomycin) can be incorporated into polydopamine-coated gold nanocages (AuNC@PDA) and that daptomycin-loaded AuNC@PDA can be conjugated to antibodies targeting a species-specific surface protein (staphylococcal protein A; Spa) as a means of achieving selective delivery of the nanoconstructs directly to the bacterial cell surface. Targeting specificity was confirmed by demonstrating a lack of binding to mammalian cells, reduced photothermal and antibiotic killing of the Spa-negative species Staphylococcus epidermidis, and reduced killing of S. aureus in the presence of unconjugated anti-Spa antibodies. We demonstrate that laser irradiation at levels within the current safety standard for use in humans can be used to achieve both a lethal photothermal effect and controlled release of the antibiotic, thus resulting in a degree of therapeutic synergy capable of eradicating viable S. aureus cells. The system was validated using planktonic bacterial cultures of both methicillin-sensitive and methicillin-resistant S. aureus strains and subsequently shown to be effective in the context of an established biofilm, thus indicating that this approach could be used to facilitate the effective treatment of intrinsically resistant biofilm infections. American Chemical Society 2016-02-10 2016-04-08 /pmc/articles/PMC4945994/ /pubmed/27441208 http://dx.doi.org/10.1021/acsinfecdis.5b00117 Text en Copyright © 2016 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle Meeker, Daniel G.
Jenkins, Samir V.
Miller, Emily K.
Beenken, Karen E.
Loughran, Allister J.
Powless, Amy
Muldoon, Timothy J.
Galanzha, Ekaterina I.
Zharov, Vladimir P.
Smeltzer, Mark S.
Chen, Jingyi
Synergistic Photothermal and Antibiotic Killing of Biofilm-Associated Staphylococcus aureus Using Targeted Antibiotic-Loaded Gold Nanoconstructs
title Synergistic Photothermal and Antibiotic Killing of Biofilm-Associated Staphylococcus aureus Using Targeted Antibiotic-Loaded Gold Nanoconstructs
title_full Synergistic Photothermal and Antibiotic Killing of Biofilm-Associated Staphylococcus aureus Using Targeted Antibiotic-Loaded Gold Nanoconstructs
title_fullStr Synergistic Photothermal and Antibiotic Killing of Biofilm-Associated Staphylococcus aureus Using Targeted Antibiotic-Loaded Gold Nanoconstructs
title_full_unstemmed Synergistic Photothermal and Antibiotic Killing of Biofilm-Associated Staphylococcus aureus Using Targeted Antibiotic-Loaded Gold Nanoconstructs
title_short Synergistic Photothermal and Antibiotic Killing of Biofilm-Associated Staphylococcus aureus Using Targeted Antibiotic-Loaded Gold Nanoconstructs
title_sort synergistic photothermal and antibiotic killing of biofilm-associated staphylococcus aureus using targeted antibiotic-loaded gold nanoconstructs
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4945994/
https://www.ncbi.nlm.nih.gov/pubmed/27441208
http://dx.doi.org/10.1021/acsinfecdis.5b00117
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