Cargando…

Eradication of Staphylococcus aureus Biofilm Infection by Persister Drug Combination

Staphylococcus aureus can cause a variety of infections, including persistent biofilm infections, which are difficult to eradicate with current antibiotic treatments. Here, we demonstrate that combining drugs that have robust anti-persister activity, such as clinafloxacin or oritavancin, in combinat...

Descripción completa

Detalles Bibliográficos
Autores principales: Yee, Rebecca, Yuan, Yuting, Tarff, Andreina, Brayton, Cory, Gour, Naina, Feng, Jie, Zhang, Ying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9598165/
https://www.ncbi.nlm.nih.gov/pubmed/36289936
http://dx.doi.org/10.3390/antibiotics11101278
_version_ 1784816264570470400
author Yee, Rebecca
Yuan, Yuting
Tarff, Andreina
Brayton, Cory
Gour, Naina
Feng, Jie
Zhang, Ying
author_facet Yee, Rebecca
Yuan, Yuting
Tarff, Andreina
Brayton, Cory
Gour, Naina
Feng, Jie
Zhang, Ying
author_sort Yee, Rebecca
collection PubMed
description Staphylococcus aureus can cause a variety of infections, including persistent biofilm infections, which are difficult to eradicate with current antibiotic treatments. Here, we demonstrate that combining drugs that have robust anti-persister activity, such as clinafloxacin or oritavancin, in combination with drugs that have high activity against growing bacteria, such as vancomycin or meropenem, could completely eradicate S. aureus biofilm bacteria in vitro. In contrast, single or two drugs, including the current treatment doxycycline plus rifampin for persistent S. aureus infection, failed to kill all biofilm bacteria in vitro. In a chronic persistent skin infection mouse model, we showed that the drug combination clinafloxacin + meropenem + daptomycin which killed all biofilm bacteria in vitro completely eradicated S. aureus biofilm infection in mice while the current treatments failed to do so. The complete eradication of biofilm bacteria is attributed to the unique high anti-persister activity of clinafloxacin, which could not be replaced by other fluoroquinolones including moxifloxacin, levofloxacin, or ciprofloxacin. We also compared our persister drug combination with the current approaches for treating persistent infections, including gentamicin + fructose and ADEP4 + rifampin in the S. aureus biofilm infection mouse model, and found neither treatment could eradicate the biofilm infection. Our study demonstrates an important treatment principle, the Yin–Yang model, for persistent infections by targeting both growing and non-growing heterogeneous bacterial populations, utilizing persister drugs for the more effective eradication of persistent and biofilm infections. Our findings have implications for the improved treatment of other persistent and biofilm infections in general.
format Online
Article
Text
id pubmed-9598165
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-95981652022-10-27 Eradication of Staphylococcus aureus Biofilm Infection by Persister Drug Combination Yee, Rebecca Yuan, Yuting Tarff, Andreina Brayton, Cory Gour, Naina Feng, Jie Zhang, Ying Antibiotics (Basel) Article Staphylococcus aureus can cause a variety of infections, including persistent biofilm infections, which are difficult to eradicate with current antibiotic treatments. Here, we demonstrate that combining drugs that have robust anti-persister activity, such as clinafloxacin or oritavancin, in combination with drugs that have high activity against growing bacteria, such as vancomycin or meropenem, could completely eradicate S. aureus biofilm bacteria in vitro. In contrast, single or two drugs, including the current treatment doxycycline plus rifampin for persistent S. aureus infection, failed to kill all biofilm bacteria in vitro. In a chronic persistent skin infection mouse model, we showed that the drug combination clinafloxacin + meropenem + daptomycin which killed all biofilm bacteria in vitro completely eradicated S. aureus biofilm infection in mice while the current treatments failed to do so. The complete eradication of biofilm bacteria is attributed to the unique high anti-persister activity of clinafloxacin, which could not be replaced by other fluoroquinolones including moxifloxacin, levofloxacin, or ciprofloxacin. We also compared our persister drug combination with the current approaches for treating persistent infections, including gentamicin + fructose and ADEP4 + rifampin in the S. aureus biofilm infection mouse model, and found neither treatment could eradicate the biofilm infection. Our study demonstrates an important treatment principle, the Yin–Yang model, for persistent infections by targeting both growing and non-growing heterogeneous bacterial populations, utilizing persister drugs for the more effective eradication of persistent and biofilm infections. Our findings have implications for the improved treatment of other persistent and biofilm infections in general. MDPI 2022-09-20 /pmc/articles/PMC9598165/ /pubmed/36289936 http://dx.doi.org/10.3390/antibiotics11101278 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yee, Rebecca
Yuan, Yuting
Tarff, Andreina
Brayton, Cory
Gour, Naina
Feng, Jie
Zhang, Ying
Eradication of Staphylococcus aureus Biofilm Infection by Persister Drug Combination
title Eradication of Staphylococcus aureus Biofilm Infection by Persister Drug Combination
title_full Eradication of Staphylococcus aureus Biofilm Infection by Persister Drug Combination
title_fullStr Eradication of Staphylococcus aureus Biofilm Infection by Persister Drug Combination
title_full_unstemmed Eradication of Staphylococcus aureus Biofilm Infection by Persister Drug Combination
title_short Eradication of Staphylococcus aureus Biofilm Infection by Persister Drug Combination
title_sort eradication of staphylococcus aureus biofilm infection by persister drug combination
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9598165/
https://www.ncbi.nlm.nih.gov/pubmed/36289936
http://dx.doi.org/10.3390/antibiotics11101278
work_keys_str_mv AT yeerebecca eradicationofstaphylococcusaureusbiofilminfectionbypersisterdrugcombination
AT yuanyuting eradicationofstaphylococcusaureusbiofilminfectionbypersisterdrugcombination
AT tarffandreina eradicationofstaphylococcusaureusbiofilminfectionbypersisterdrugcombination
AT braytoncory eradicationofstaphylococcusaureusbiofilminfectionbypersisterdrugcombination
AT gournaina eradicationofstaphylococcusaureusbiofilminfectionbypersisterdrugcombination
AT fengjie eradicationofstaphylococcusaureusbiofilminfectionbypersisterdrugcombination
AT zhangying eradicationofstaphylococcusaureusbiofilminfectionbypersisterdrugcombination