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Auranofin Has Advantages over First-Line Drugs in the Treatment of Severe Streptococcus suis Infections
Streptococcal toxic shock-like syndrome (STSLS) likely occurs when an individual is infected with the Streptococcus suis (S. suis) epidemic strain and is characterized by a cytokine storm, multiple organ dysfunction syndrome (MODS) and a high incidence of mortality despite adequate treatment. A numb...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823847/ https://www.ncbi.nlm.nih.gov/pubmed/33396878 http://dx.doi.org/10.3390/antibiotics10010026 |
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author | Lu, Hao Lu, Wenjia Zhu, Yongwei Wang, Chenchen Shi, Liming Li, Xiaodan Wu, Zhaoyuan Wang, Gaoyan Dong, Wenqi Tan, Chen Liu, Manli |
author_facet | Lu, Hao Lu, Wenjia Zhu, Yongwei Wang, Chenchen Shi, Liming Li, Xiaodan Wu, Zhaoyuan Wang, Gaoyan Dong, Wenqi Tan, Chen Liu, Manli |
author_sort | Lu, Hao |
collection | PubMed |
description | Streptococcal toxic shock-like syndrome (STSLS) likely occurs when an individual is infected with the Streptococcus suis (S. suis) epidemic strain and is characterized by a cytokine storm, multiple organ dysfunction syndrome (MODS) and a high incidence of mortality despite adequate treatment. A number of antibiotics exhibit excellent bactericidal effects in vivo, such as fluoroquinolones, aminoglycosides (gentamicin) and β-lactams (penicillin G, ceftiofur, or amoxicillin), but are less effective for treating STSLS. Therefore, there is an urgent need to identify new compounds that can reduce the damage caused by STSLS. In the present study, we identified auranofin, an orally bioavailable FDA-approved anti-rheumatic drug as a candidate repurposed drug to treat severe S. suis infections. Our results showed that auranofin can bind to the functional domain of bacterial thioredoxin reductase, decreasing the reducing redox-responsive capacity of target bacteria and allowing for the killing of S. suis cells. We also observed that auranofin has antibacterial activity against other gram-positive bacteria, such as multidrug resistant Streptococcus pneumoniae (MDRSP), Streptococcus agalactiae, and vancomycin-resistant strains of Staphylococcus aureus. Additionally, auranofin is capable of eradicating intracellular S.suis present inside infected macrophage cells. Mouse model experimental results showed that auranofin could effectively reduce the mortality of mice infected with S. suis. Compared to the ampicillin treatment group, the survival rate of mice in the auranofin treatment group in severely infected model mice was significantly improved. These results suggest that auranofin has the potential for use as an effective antibiotic against S. suis. |
format | Online Article Text |
id | pubmed-7823847 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-78238472021-01-24 Auranofin Has Advantages over First-Line Drugs in the Treatment of Severe Streptococcus suis Infections Lu, Hao Lu, Wenjia Zhu, Yongwei Wang, Chenchen Shi, Liming Li, Xiaodan Wu, Zhaoyuan Wang, Gaoyan Dong, Wenqi Tan, Chen Liu, Manli Antibiotics (Basel) Article Streptococcal toxic shock-like syndrome (STSLS) likely occurs when an individual is infected with the Streptococcus suis (S. suis) epidemic strain and is characterized by a cytokine storm, multiple organ dysfunction syndrome (MODS) and a high incidence of mortality despite adequate treatment. A number of antibiotics exhibit excellent bactericidal effects in vivo, such as fluoroquinolones, aminoglycosides (gentamicin) and β-lactams (penicillin G, ceftiofur, or amoxicillin), but are less effective for treating STSLS. Therefore, there is an urgent need to identify new compounds that can reduce the damage caused by STSLS. In the present study, we identified auranofin, an orally bioavailable FDA-approved anti-rheumatic drug as a candidate repurposed drug to treat severe S. suis infections. Our results showed that auranofin can bind to the functional domain of bacterial thioredoxin reductase, decreasing the reducing redox-responsive capacity of target bacteria and allowing for the killing of S. suis cells. We also observed that auranofin has antibacterial activity against other gram-positive bacteria, such as multidrug resistant Streptococcus pneumoniae (MDRSP), Streptococcus agalactiae, and vancomycin-resistant strains of Staphylococcus aureus. Additionally, auranofin is capable of eradicating intracellular S.suis present inside infected macrophage cells. Mouse model experimental results showed that auranofin could effectively reduce the mortality of mice infected with S. suis. Compared to the ampicillin treatment group, the survival rate of mice in the auranofin treatment group in severely infected model mice was significantly improved. These results suggest that auranofin has the potential for use as an effective antibiotic against S. suis. MDPI 2020-12-30 /pmc/articles/PMC7823847/ /pubmed/33396878 http://dx.doi.org/10.3390/antibiotics10010026 Text en © 2020 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 Lu, Hao Lu, Wenjia Zhu, Yongwei Wang, Chenchen Shi, Liming Li, Xiaodan Wu, Zhaoyuan Wang, Gaoyan Dong, Wenqi Tan, Chen Liu, Manli Auranofin Has Advantages over First-Line Drugs in the Treatment of Severe Streptococcus suis Infections |
title | Auranofin Has Advantages over First-Line Drugs in the Treatment of Severe Streptococcus suis Infections |
title_full | Auranofin Has Advantages over First-Line Drugs in the Treatment of Severe Streptococcus suis Infections |
title_fullStr | Auranofin Has Advantages over First-Line Drugs in the Treatment of Severe Streptococcus suis Infections |
title_full_unstemmed | Auranofin Has Advantages over First-Line Drugs in the Treatment of Severe Streptococcus suis Infections |
title_short | Auranofin Has Advantages over First-Line Drugs in the Treatment of Severe Streptococcus suis Infections |
title_sort | auranofin has advantages over first-line drugs in the treatment of severe streptococcus suis infections |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823847/ https://www.ncbi.nlm.nih.gov/pubmed/33396878 http://dx.doi.org/10.3390/antibiotics10010026 |
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