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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...

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Autores principales: Lu, Hao, Lu, Wenjia, Zhu, Yongwei, Wang, Chenchen, Shi, Liming, Li, Xiaodan, Wu, Zhaoyuan, Wang, Gaoyan, Dong, Wenqi, Tan, Chen, Liu, Manli
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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.
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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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