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Ellagic Acid Derivatives from Rubus ulmifolius Inhibit Staphylococcus aureus Biofilm Formation and Improve Response to Antibiotics

BACKGROUND: Biofilms contribute to the pathogenesis of many forms of Staphylococcus aureus infection. Treatment of these infections is complicated by intrinsic resistance to conventional antibiotics, thus creating an urgent need for strategies that can be used for the prevention and treatment of bio...

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Autores principales: Quave, Cassandra L., Estévez-Carmona, Miriam, Compadre, Cesar M., Hobby, Gerren, Hendrickson, Howard, Beenken, Karen E., Smeltzer, Mark S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3252291/
https://www.ncbi.nlm.nih.gov/pubmed/22242149
http://dx.doi.org/10.1371/journal.pone.0028737
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author Quave, Cassandra L.
Estévez-Carmona, Miriam
Compadre, Cesar M.
Hobby, Gerren
Hendrickson, Howard
Beenken, Karen E.
Smeltzer, Mark S.
author_facet Quave, Cassandra L.
Estévez-Carmona, Miriam
Compadre, Cesar M.
Hobby, Gerren
Hendrickson, Howard
Beenken, Karen E.
Smeltzer, Mark S.
author_sort Quave, Cassandra L.
collection PubMed
description BACKGROUND: Biofilms contribute to the pathogenesis of many forms of Staphylococcus aureus infection. Treatment of these infections is complicated by intrinsic resistance to conventional antibiotics, thus creating an urgent need for strategies that can be used for the prevention and treatment of biofilm-associated infections. METHODOLOGY/PRINCIPAL FINDINGS: This study demonstrates that a botanical natural product composition (220D-F2) rich in ellagic acid and its derivatives can limit S. aureus biofilm formation to a degree that can be correlated with increased antibiotic susceptibility. The source of this composition is Rubus ulmifolius Schott. (Rosaceae), a plant used in complementary and alternative medicine in southern Italy for the treatment of skin and soft tissue infections. All S. aureus clonal lineages tested exhibited a reduced capacity to form a biofilm at 220D-F2 concentrations ranging from 50–200 µg/mL, which were well below the concentrations required to limit bacterial growth (530–1040 µg/mL). This limitation was therapeutically relevant in that inclusion of 220D-F2 resulted in enhanced susceptibility to the functionally-distinct antibiotics daptomycin, clindamycin and oxacillin. Testing with kidney and liver cell lines also demonstrated a lack of host cell cytotoxicity at concentrations of 220D-F2 required to achieve these effects. CONCLUSIONS/SIGNIFICANCE: These results demonstrate that extract 220D-F2 from the root of Rubus ulmifolius can be used to inhibit S. aureus biofilm formation to a degree that can be correlated with increased antibiotic susceptibility without toxic effects on normal mammalian cells. Hence, 220D-F2 is a strong candidate for development as a botanical drug for use in the prevention and treatment of S. aureus biofilm-associated infections.
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spelling pubmed-32522912012-01-12 Ellagic Acid Derivatives from Rubus ulmifolius Inhibit Staphylococcus aureus Biofilm Formation and Improve Response to Antibiotics Quave, Cassandra L. Estévez-Carmona, Miriam Compadre, Cesar M. Hobby, Gerren Hendrickson, Howard Beenken, Karen E. Smeltzer, Mark S. PLoS One Research Article BACKGROUND: Biofilms contribute to the pathogenesis of many forms of Staphylococcus aureus infection. Treatment of these infections is complicated by intrinsic resistance to conventional antibiotics, thus creating an urgent need for strategies that can be used for the prevention and treatment of biofilm-associated infections. METHODOLOGY/PRINCIPAL FINDINGS: This study demonstrates that a botanical natural product composition (220D-F2) rich in ellagic acid and its derivatives can limit S. aureus biofilm formation to a degree that can be correlated with increased antibiotic susceptibility. The source of this composition is Rubus ulmifolius Schott. (Rosaceae), a plant used in complementary and alternative medicine in southern Italy for the treatment of skin and soft tissue infections. All S. aureus clonal lineages tested exhibited a reduced capacity to form a biofilm at 220D-F2 concentrations ranging from 50–200 µg/mL, which were well below the concentrations required to limit bacterial growth (530–1040 µg/mL). This limitation was therapeutically relevant in that inclusion of 220D-F2 resulted in enhanced susceptibility to the functionally-distinct antibiotics daptomycin, clindamycin and oxacillin. Testing with kidney and liver cell lines also demonstrated a lack of host cell cytotoxicity at concentrations of 220D-F2 required to achieve these effects. CONCLUSIONS/SIGNIFICANCE: These results demonstrate that extract 220D-F2 from the root of Rubus ulmifolius can be used to inhibit S. aureus biofilm formation to a degree that can be correlated with increased antibiotic susceptibility without toxic effects on normal mammalian cells. Hence, 220D-F2 is a strong candidate for development as a botanical drug for use in the prevention and treatment of S. aureus biofilm-associated infections. Public Library of Science 2012-01-05 /pmc/articles/PMC3252291/ /pubmed/22242149 http://dx.doi.org/10.1371/journal.pone.0028737 Text en Quave et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Quave, Cassandra L.
Estévez-Carmona, Miriam
Compadre, Cesar M.
Hobby, Gerren
Hendrickson, Howard
Beenken, Karen E.
Smeltzer, Mark S.
Ellagic Acid Derivatives from Rubus ulmifolius Inhibit Staphylococcus aureus Biofilm Formation and Improve Response to Antibiotics
title Ellagic Acid Derivatives from Rubus ulmifolius Inhibit Staphylococcus aureus Biofilm Formation and Improve Response to Antibiotics
title_full Ellagic Acid Derivatives from Rubus ulmifolius Inhibit Staphylococcus aureus Biofilm Formation and Improve Response to Antibiotics
title_fullStr Ellagic Acid Derivatives from Rubus ulmifolius Inhibit Staphylococcus aureus Biofilm Formation and Improve Response to Antibiotics
title_full_unstemmed Ellagic Acid Derivatives from Rubus ulmifolius Inhibit Staphylococcus aureus Biofilm Formation and Improve Response to Antibiotics
title_short Ellagic Acid Derivatives from Rubus ulmifolius Inhibit Staphylococcus aureus Biofilm Formation and Improve Response to Antibiotics
title_sort ellagic acid derivatives from rubus ulmifolius inhibit staphylococcus aureus biofilm formation and improve response to antibiotics
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3252291/
https://www.ncbi.nlm.nih.gov/pubmed/22242149
http://dx.doi.org/10.1371/journal.pone.0028737
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