Simeprevir restores the anti-Staphylococcus activity of polymyxins
Abstract Methicillin-resistant Staphylococcus aureus (MRSA) infection poses a severe threat to global public health due to its high mortality. Currently, polymyxins are mainly used for the treatment of Gram-negative bacterial-related infection, while exhibiting limited antibacterial activities again...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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SpringerOpen
2023-11-01
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| Series: | AMB Express |
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| Online Access: | https://doi.org/10.1186/s13568-023-01634-8 |
| _version_ | 1797636660655030272 |
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| author | Yuan Wu Pingyun Wu Ruolan Wu Huilong Li Yao Duan Chaoni Cai Zixin Liu Pengfei She Di Zhang |
| author_facet | Yuan Wu Pingyun Wu Ruolan Wu Huilong Li Yao Duan Chaoni Cai Zixin Liu Pengfei She Di Zhang |
| author_sort | Yuan Wu |
| collection | DOAJ |
| description | Abstract Methicillin-resistant Staphylococcus aureus (MRSA) infection poses a severe threat to global public health due to its high mortality. Currently, polymyxins are mainly used for the treatment of Gram-negative bacterial-related infection, while exhibiting limited antibacterial activities against Staphylococcus aureus (S. aureus). However, the combination of antibiotics with antibiotic adjuvants is a feasible strategy for the hard-treated infection and toxicity reducing. We will investigate the antibacterial activity of simeprevir (SIM), which treated for genotype 1 and 4 chronic hepatitis C, combined with polymyxins against MRSA through high-throughput screening technology. In our study, the synergistic antibacterial effect of SIM and polymyxins against S. aureus in vitro was found by checkerboard assay and time-growth curve. The cytotoxicity of SIM combined with polymyxin B sulfate [PB(S)] or polymyxin E (PE) in vitro was evaluated using CCK-8, human RBC hemolysis and scratch assays. In addition, we investigated the eradication of biofilm formation of S. aureus by biofilm inhibition assay and the killing of persister cells. Moreover, we evaluated the therapeutic effect and in vivo toxicity of the combination against MRSA in murine subcutaneous abscess model. Furthermore, it was preliminarily found that SIM significantly enhanced the destruction of MRSA membrane by SYTOX Green and DISC3(5) probes. In summary, these results reveal that the therapy of SIM combined with polymyxins (especially PE) is promising for the treatment of MRSA infection. |
| first_indexed | 2024-03-11T12:37:13Z |
| format | Article |
| id | doaj.art-084e7f24b017455b9efcf31ddc022643 |
| institution | Directory Open Access Journal |
| issn | 2191-0855 |
| language | English |
| last_indexed | 2024-03-11T12:37:13Z |
| publishDate | 2023-11-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | AMB Express |
| spelling | doaj.art-084e7f24b017455b9efcf31ddc0226432023-11-05T12:30:24ZengSpringerOpenAMB Express2191-08552023-11-0113111410.1186/s13568-023-01634-8Simeprevir restores the anti-Staphylococcus activity of polymyxinsYuan Wu0Pingyun Wu1Ruolan Wu2Huilong Li3Yao Duan4Chaoni Cai5Zixin Liu6Pengfei She7Di Zhang8Department of Laboratory Medicine, The Third Xiangya Hospital of Central South UniversityDepartment of Laboratory Medicine, The Third Xiangya Hospital of Central South UniversityDepartment of Laboratory Medicine, The Third Xiangya Hospital of Central South UniversityDepartment of Laboratory Medicine, The Third Xiangya Hospital of Central South UniversityDepartment of Laboratory Medicine, The Third Xiangya Hospital of Central South UniversityDepartment of Laboratory Medicine, The Third Xiangya Hospital of Central South UniversityDepartment of Laboratory Medicine, The Third Xiangya Hospital of Central South UniversityDepartment of Laboratory Medicine, The Third Xiangya Hospital of Central South UniversityDepartment of Laboratory Medicine, The Third Xiangya Hospital of Central South UniversityAbstract Methicillin-resistant Staphylococcus aureus (MRSA) infection poses a severe threat to global public health due to its high mortality. Currently, polymyxins are mainly used for the treatment of Gram-negative bacterial-related infection, while exhibiting limited antibacterial activities against Staphylococcus aureus (S. aureus). However, the combination of antibiotics with antibiotic adjuvants is a feasible strategy for the hard-treated infection and toxicity reducing. We will investigate the antibacterial activity of simeprevir (SIM), which treated for genotype 1 and 4 chronic hepatitis C, combined with polymyxins against MRSA through high-throughput screening technology. In our study, the synergistic antibacterial effect of SIM and polymyxins against S. aureus in vitro was found by checkerboard assay and time-growth curve. The cytotoxicity of SIM combined with polymyxin B sulfate [PB(S)] or polymyxin E (PE) in vitro was evaluated using CCK-8, human RBC hemolysis and scratch assays. In addition, we investigated the eradication of biofilm formation of S. aureus by biofilm inhibition assay and the killing of persister cells. Moreover, we evaluated the therapeutic effect and in vivo toxicity of the combination against MRSA in murine subcutaneous abscess model. Furthermore, it was preliminarily found that SIM significantly enhanced the destruction of MRSA membrane by SYTOX Green and DISC3(5) probes. In summary, these results reveal that the therapy of SIM combined with polymyxins (especially PE) is promising for the treatment of MRSA infection.https://doi.org/10.1186/s13568-023-01634-8Staphylococcus aureusSimeprevirPolymyxinsAntimicrobialDrug repurposingPersister cells |
| spellingShingle | Yuan Wu Pingyun Wu Ruolan Wu Huilong Li Yao Duan Chaoni Cai Zixin Liu Pengfei She Di Zhang Simeprevir restores the anti-Staphylococcus activity of polymyxins AMB Express Staphylococcus aureus Simeprevir Polymyxins Antimicrobial Drug repurposing Persister cells |
| title | Simeprevir restores the anti-Staphylococcus activity of polymyxins |
| title_full | Simeprevir restores the anti-Staphylococcus activity of polymyxins |
| title_fullStr | Simeprevir restores the anti-Staphylococcus activity of polymyxins |
| title_full_unstemmed | Simeprevir restores the anti-Staphylococcus activity of polymyxins |
| title_short | Simeprevir restores the anti-Staphylococcus activity of polymyxins |
| title_sort | simeprevir restores the anti staphylococcus activity of polymyxins |
| topic | Staphylococcus aureus Simeprevir Polymyxins Antimicrobial Drug repurposing Persister cells |
| url | https://doi.org/10.1186/s13568-023-01634-8 |
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