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...
Autores principales: | , , , , , , |
---|---|
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 |