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Streptokinase Treatment Reverses Biofilm-Associated Antibiotic Resistance in Staphylococcus aureus

Biofilms formed by Staphylococcus aureus is a serious complication to the use of medical implants. A central part of the pathogenesis relies on S. aureus’ ability to adhere to host extracellular matrix proteins, which adsorb to medical implants and stimulate biofilm formation. Being coagulase positi...

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Autores principales: Jørgensen, Nis Pedersen, Zobek, Natalia, Dreier, Cindy, Haaber, Jakob, Ingmer, Hanne, Larsen, Ole Halfdan, Meyer, Rikke L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5039596/
https://www.ncbi.nlm.nih.gov/pubmed/27681928
http://dx.doi.org/10.3390/microorganisms4030036
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author Jørgensen, Nis Pedersen
Zobek, Natalia
Dreier, Cindy
Haaber, Jakob
Ingmer, Hanne
Larsen, Ole Halfdan
Meyer, Rikke L.
author_facet Jørgensen, Nis Pedersen
Zobek, Natalia
Dreier, Cindy
Haaber, Jakob
Ingmer, Hanne
Larsen, Ole Halfdan
Meyer, Rikke L.
author_sort Jørgensen, Nis Pedersen
collection PubMed
description Biofilms formed by Staphylococcus aureus is a serious complication to the use of medical implants. A central part of the pathogenesis relies on S. aureus’ ability to adhere to host extracellular matrix proteins, which adsorb to medical implants and stimulate biofilm formation. Being coagulase positive, S. aureus furthermore induces formation of fibrin fibers from fibrinogen in the blood. Consequently, we hypothesized that fibrin is a key component of the extracellular matrix of S. aureus biofilms under in vivo conditions, and that the recalcitrance of biofilm infections can be overcome by combining antibiotic treatment with a fibrinolytic drug. We quantified S. aureus USA300 biofilms grown on peg-lids in brain heart infusion (BHI) broth with 0%–50% human plasma. Young (2 h) and mature (24 h) biofilms were then treated with streptokinase to determine if this lead to dispersal. Then, the minimal biofilm eradication concentration (MBEC) of 24 h old biofilms was measured for vancomycin and daptomycin alone or in combination with 10 µg/mL rifampicin in the presence or absence of streptokinase in the antibiotic treatment step. Finally, biofilms were visualized by confocal laser scanning microscopy. Addition of human plasma stimulated biofilm formation in BHI in a dose-dependent manner, and biofilms could be partially dispersed by streptokinase. The biofilms could be eradicated with physiologically relevant concentrations of streptokinase in combination with rifampicin and vancomycin or daptomycin, which are commonly used antibiotics for treatment of S. aureus infections. Fibronolytic drugs have been used to treat thromboembolic events for decades, and our findings suggest that their use against biofilm infections has the potential to improve the efficacy of antibiotics in treatment of S. aureus biofilm infections.
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spelling pubmed-50395962016-09-28 Streptokinase Treatment Reverses Biofilm-Associated Antibiotic Resistance in Staphylococcus aureus Jørgensen, Nis Pedersen Zobek, Natalia Dreier, Cindy Haaber, Jakob Ingmer, Hanne Larsen, Ole Halfdan Meyer, Rikke L. Microorganisms Article Biofilms formed by Staphylococcus aureus is a serious complication to the use of medical implants. A central part of the pathogenesis relies on S. aureus’ ability to adhere to host extracellular matrix proteins, which adsorb to medical implants and stimulate biofilm formation. Being coagulase positive, S. aureus furthermore induces formation of fibrin fibers from fibrinogen in the blood. Consequently, we hypothesized that fibrin is a key component of the extracellular matrix of S. aureus biofilms under in vivo conditions, and that the recalcitrance of biofilm infections can be overcome by combining antibiotic treatment with a fibrinolytic drug. We quantified S. aureus USA300 biofilms grown on peg-lids in brain heart infusion (BHI) broth with 0%–50% human plasma. Young (2 h) and mature (24 h) biofilms were then treated with streptokinase to determine if this lead to dispersal. Then, the minimal biofilm eradication concentration (MBEC) of 24 h old biofilms was measured for vancomycin and daptomycin alone or in combination with 10 µg/mL rifampicin in the presence or absence of streptokinase in the antibiotic treatment step. Finally, biofilms were visualized by confocal laser scanning microscopy. Addition of human plasma stimulated biofilm formation in BHI in a dose-dependent manner, and biofilms could be partially dispersed by streptokinase. The biofilms could be eradicated with physiologically relevant concentrations of streptokinase in combination with rifampicin and vancomycin or daptomycin, which are commonly used antibiotics for treatment of S. aureus infections. Fibronolytic drugs have been used to treat thromboembolic events for decades, and our findings suggest that their use against biofilm infections has the potential to improve the efficacy of antibiotics in treatment of S. aureus biofilm infections. MDPI 2016-09-20 /pmc/articles/PMC5039596/ /pubmed/27681928 http://dx.doi.org/10.3390/microorganisms4030036 Text en © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Jørgensen, Nis Pedersen
Zobek, Natalia
Dreier, Cindy
Haaber, Jakob
Ingmer, Hanne
Larsen, Ole Halfdan
Meyer, Rikke L.
Streptokinase Treatment Reverses Biofilm-Associated Antibiotic Resistance in Staphylococcus aureus
title Streptokinase Treatment Reverses Biofilm-Associated Antibiotic Resistance in Staphylococcus aureus
title_full Streptokinase Treatment Reverses Biofilm-Associated Antibiotic Resistance in Staphylococcus aureus
title_fullStr Streptokinase Treatment Reverses Biofilm-Associated Antibiotic Resistance in Staphylococcus aureus
title_full_unstemmed Streptokinase Treatment Reverses Biofilm-Associated Antibiotic Resistance in Staphylococcus aureus
title_short Streptokinase Treatment Reverses Biofilm-Associated Antibiotic Resistance in Staphylococcus aureus
title_sort streptokinase treatment reverses biofilm-associated antibiotic resistance in staphylococcus aureus
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5039596/
https://www.ncbi.nlm.nih.gov/pubmed/27681928
http://dx.doi.org/10.3390/microorganisms4030036
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