Auranofin Has Advantages over First-Line Drugs in the Treatment of Severe <i>Streptococcus suis</i> Infections
Streptococcal toxic shock-like syndrome (STSLS) likely occurs when an individual is infected with the <i>Streptococcus suis</i> (<i>S. suis</i>) epidemic strain and is characterized by a cytokine storm, multiple organ dysfunction syndrome (MODS) and a high incidence of mortal...
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MDPI AG
2020-12-01
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| Series: | Antibiotics |
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| Online Access: | https://www.mdpi.com/2079-6382/10/1/26 |
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| author | Hao Lu Wenjia Lu Yongwei Zhu Chenchen Wang Liming Shi Xiaodan Li Zhaoyuan Wu Gaoyan Wang Wenqi Dong Chen Tan Manli Liu |
| author_facet | Hao Lu Wenjia Lu Yongwei Zhu Chenchen Wang Liming Shi Xiaodan Li Zhaoyuan Wu Gaoyan Wang Wenqi Dong Chen Tan Manli Liu |
| author_sort | Hao Lu |
| collection | DOAJ |
| description | Streptococcal toxic shock-like syndrome (STSLS) likely occurs when an individual is infected with the <i>Streptococcus suis</i> (<i>S. suis</i>) 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 <i>S. suis</i> 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 <i>S. suis</i> 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 <i>S.suis</i> present inside infected macrophage cells. Mouse model experimental results showed that auranofin could effectively reduce the mortality of mice infected with <i>S. suis</i>. 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 <i>S. suis.</i> |
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| language | English |
| last_indexed | 2024-03-10T13:39:42Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
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| series | Antibiotics |
| spelling | doaj.art-73699b32b44541e1bc8588acfed5b58e2023-11-21T03:10:48ZengMDPI AGAntibiotics2079-63822020-12-011012610.3390/antibiotics10010026Auranofin Has Advantages over First-Line Drugs in the Treatment of Severe <i>Streptococcus suis</i> InfectionsHao Lu0Wenjia Lu1Yongwei Zhu2Chenchen Wang3Liming Shi4Xiaodan Li5Zhaoyuan Wu6Gaoyan Wang7Wenqi Dong8Chen Tan9Manli Liu10State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, ChinaState Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, ChinaState Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, ChinaState Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, ChinaHeze Municipal Hospital, Heze 274000, ChinaState Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, ChinaHubei Biopesticide Engineering Research Centre, Wuhan 430070, ChinaState Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, ChinaState Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, ChinaState Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, ChinaHubei Biopesticide Engineering Research Centre, Wuhan 430070, ChinaStreptococcal toxic shock-like syndrome (STSLS) likely occurs when an individual is infected with the <i>Streptococcus suis</i> (<i>S. suis</i>) 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 <i>S. suis</i> 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 <i>S. suis</i> 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 <i>S.suis</i> present inside infected macrophage cells. Mouse model experimental results showed that auranofin could effectively reduce the mortality of mice infected with <i>S. suis</i>. 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 <i>S. suis.</i>https://www.mdpi.com/2079-6382/10/1/26STSLS<i>Streptococcus suis</i>auranofinmolecular docking |
| spellingShingle | Hao Lu Wenjia Lu Yongwei Zhu Chenchen Wang Liming Shi Xiaodan Li Zhaoyuan Wu Gaoyan Wang Wenqi Dong Chen Tan Manli Liu Auranofin Has Advantages over First-Line Drugs in the Treatment of Severe <i>Streptococcus suis</i> Infections Antibiotics STSLS <i>Streptococcus suis</i> auranofin molecular docking |
| title | Auranofin Has Advantages over First-Line Drugs in the Treatment of Severe <i>Streptococcus suis</i> Infections |
| title_full | Auranofin Has Advantages over First-Line Drugs in the Treatment of Severe <i>Streptococcus suis</i> Infections |
| title_fullStr | Auranofin Has Advantages over First-Line Drugs in the Treatment of Severe <i>Streptococcus suis</i> Infections |
| title_full_unstemmed | Auranofin Has Advantages over First-Line Drugs in the Treatment of Severe <i>Streptococcus suis</i> Infections |
| title_short | Auranofin Has Advantages over First-Line Drugs in the Treatment of Severe <i>Streptococcus suis</i> Infections |
| title_sort | auranofin has advantages over first line drugs in the treatment of severe i streptococcus suis i infections |
| topic | STSLS <i>Streptococcus suis</i> auranofin molecular docking |
| url | https://www.mdpi.com/2079-6382/10/1/26 |
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