Synergistic Antimicrobial Effects of Silver/Transition-metal Combinatorial Treatments

Abstract Due to the emergence of multi-drug resistant strains, development of novel antibiotics has become a critical issue. One promising approach is the use of transition metals, since they exhibit rapid and significant toxicity, at low concentrations, in prokaryotic cells. Nevertheless, one main...

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Autores principales: Javier A. Garza-Cervantes, Arturo Chávez-Reyes, Elena C. Castillo, Gerardo García-Rivas, Oscar Antonio Ortega-Rivera, Eva Salinas, Margarita Ortiz-Martínez, Sara Leticia Gómez-Flores, Jorge A. Peña-Martínez, Alan Pepi-Molina, Mario T. Treviño-González, Xristo Zarate, María Elena Cantú-Cárdenas, Carlos Enrique Escarcega-Gonzalez, J. Rubén Morones-Ramírez
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Publicado: Nature Portfolio 2017
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spelling oai:doaj.org-article:50210ea949b4482c82be7e858a2774512021-12-02T12:31:53ZSynergistic Antimicrobial Effects of Silver/Transition-metal Combinatorial Treatments10.1038/s41598-017-01017-72045-2322https://doaj.org/article/50210ea949b4482c82be7e858a2774512017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01017-7https://doaj.org/toc/2045-2322Abstract Due to the emergence of multi-drug resistant strains, development of novel antibiotics has become a critical issue. One promising approach is the use of transition metals, since they exhibit rapid and significant toxicity, at low concentrations, in prokaryotic cells. Nevertheless, one main drawback of transition metals is their toxicity in eukaryotic cells. Here, we show that the barriers to use them as therapeutic agents could be mitigated by combining them with silver. We demonstrate that synergism of combinatorial treatments (Silver/transition metals, including Zn, Co, Cd, Ni, and Cu) increases up to 8-fold their antimicrobial effect, when compared to their individual effects, against E. coli and B. subtilis. We find that most combinatorial treatments exhibit synergistic antimicrobial effects at low/non-toxic concentrations to human keratinocyte cells, blast and melanoma rat cell lines. Moreover, we show that silver/(Cu, Ni, and Zn) increase prokaryotic cell permeability at sub-inhibitory concentrations, demonstrating this to be a possible mechanism of the synergistic behavior. Together, these results suggest that these combinatorial treatments will play an important role in the future development of antimicrobial agents and treatments against infections. In specific, the cytotoxicity experiments show that the combinations have great potential in the treatment of topical infections.Javier A. Garza-CervantesArturo Chávez-ReyesElena C. CastilloGerardo García-RivasOscar Antonio Ortega-RiveraEva SalinasMargarita Ortiz-MartínezSara Leticia Gómez-FloresJorge A. Peña-MartínezAlan Pepi-MolinaMario T. Treviño-GonzálezXristo ZarateMaría Elena Cantú-CárdenasCarlos Enrique Escarcega-GonzalezJ. Rubén Morones-RamírezNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-16 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Javier A. Garza-Cervantes
Arturo Chávez-Reyes
Elena C. Castillo
Gerardo García-Rivas
Oscar Antonio Ortega-Rivera
Eva Salinas
Margarita Ortiz-Martínez
Sara Leticia Gómez-Flores
Jorge A. Peña-Martínez
Alan Pepi-Molina
Mario T. Treviño-González
Xristo Zarate
María Elena Cantú-Cárdenas
Carlos Enrique Escarcega-Gonzalez
J. Rubén Morones-Ramírez
Synergistic Antimicrobial Effects of Silver/Transition-metal Combinatorial Treatments
description Abstract Due to the emergence of multi-drug resistant strains, development of novel antibiotics has become a critical issue. One promising approach is the use of transition metals, since they exhibit rapid and significant toxicity, at low concentrations, in prokaryotic cells. Nevertheless, one main drawback of transition metals is their toxicity in eukaryotic cells. Here, we show that the barriers to use them as therapeutic agents could be mitigated by combining them with silver. We demonstrate that synergism of combinatorial treatments (Silver/transition metals, including Zn, Co, Cd, Ni, and Cu) increases up to 8-fold their antimicrobial effect, when compared to their individual effects, against E. coli and B. subtilis. We find that most combinatorial treatments exhibit synergistic antimicrobial effects at low/non-toxic concentrations to human keratinocyte cells, blast and melanoma rat cell lines. Moreover, we show that silver/(Cu, Ni, and Zn) increase prokaryotic cell permeability at sub-inhibitory concentrations, demonstrating this to be a possible mechanism of the synergistic behavior. Together, these results suggest that these combinatorial treatments will play an important role in the future development of antimicrobial agents and treatments against infections. In specific, the cytotoxicity experiments show that the combinations have great potential in the treatment of topical infections.
format article
author Javier A. Garza-Cervantes
Arturo Chávez-Reyes
Elena C. Castillo
Gerardo García-Rivas
Oscar Antonio Ortega-Rivera
Eva Salinas
Margarita Ortiz-Martínez
Sara Leticia Gómez-Flores
Jorge A. Peña-Martínez
Alan Pepi-Molina
Mario T. Treviño-González
Xristo Zarate
María Elena Cantú-Cárdenas
Carlos Enrique Escarcega-Gonzalez
J. Rubén Morones-Ramírez
author_facet Javier A. Garza-Cervantes
Arturo Chávez-Reyes
Elena C. Castillo
Gerardo García-Rivas
Oscar Antonio Ortega-Rivera
Eva Salinas
Margarita Ortiz-Martínez
Sara Leticia Gómez-Flores
Jorge A. Peña-Martínez
Alan Pepi-Molina
Mario T. Treviño-González
Xristo Zarate
María Elena Cantú-Cárdenas
Carlos Enrique Escarcega-Gonzalez
J. Rubén Morones-Ramírez
author_sort Javier A. Garza-Cervantes
title Synergistic Antimicrobial Effects of Silver/Transition-metal Combinatorial Treatments
title_short Synergistic Antimicrobial Effects of Silver/Transition-metal Combinatorial Treatments
title_full Synergistic Antimicrobial Effects of Silver/Transition-metal Combinatorial Treatments
title_fullStr Synergistic Antimicrobial Effects of Silver/Transition-metal Combinatorial Treatments
title_full_unstemmed Synergistic Antimicrobial Effects of Silver/Transition-metal Combinatorial Treatments
title_sort synergistic antimicrobial effects of silver/transition-metal combinatorial treatments
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/50210ea949b4482c82be7e858a277451
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