The Inhibition Effect of Linezolid With Reyanning Mixture on MRSA and its Biofilm is More Significant than That of Linezolid Alone
Methicillin-resistant Staphylococcus aureus (MRSA) is a superbacterium, and when it forms biofilms, it is difficult to treat even with the first-line of antibiotic linezolid (LNZ). Reyanning mixture (RYN), a compound-based Chinese medicine formula, has been found to have inhibitory effects on biofil...
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| Format: | Article |
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Frontiers Media S.A.
2022-01-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.766309/full |
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| author | Lulu Zhang Lulu Zhang Weifeng Yang Yajun Chu Bo Wen Yungchi Cheng Tariq Mahmood Mei Bao Mei Bao Feng Ge Li Li Jianfeng Yi Chengqiang Du Cheng Lu Yong Tan |
| author_facet | Lulu Zhang Lulu Zhang Weifeng Yang Yajun Chu Bo Wen Yungchi Cheng Tariq Mahmood Mei Bao Mei Bao Feng Ge Li Li Jianfeng Yi Chengqiang Du Cheng Lu Yong Tan |
| author_sort | Lulu Zhang |
| collection | DOAJ |
| description | Methicillin-resistant Staphylococcus aureus (MRSA) is a superbacterium, and when it forms biofilms, it is difficult to treat even with the first-line of antibiotic linezolid (LNZ). Reyanning mixture (RYN), a compound-based Chinese medicine formula, has been found to have inhibitory effects on biofilms. This study aims to explore the synergistic inhibitory effect and corresponding mechanisms of their (LNZ&RYN) combination on the planktonic as well as biofilm cells of MRSA. Broth microdilution and chessboard methods were employed for the determination of minimum inhibitory concentrations (MICs) and synergistic concentration of LNZ&RYN, respectively. The effect of the combined medication on biofilm and mature biofilm of MRSA were observed by biofilm morphology and permeability experiments, respectively. To unveil the molecular mechanism of action of the synergistic combination of LNZ and RYN, RT-PCR based biofilm-related gene expression analysis and ultra-high pressure liquid chromatography-time-of-flight mass spectrometry based endogenous metabonomic analysis were deployed. The results indicated that 1/16RYN as the best combined dose reduced LNZ (4 μg/ml) to 2 μg/ml. The combined treatment inhibited living MRSA before and after biofilm formation, removed the residual structure of dead bacteria in MRSA biofilms and affected the shape and size of bacteria, resulting in the improvement of biofilm permeability. The mechanism was that biofilm-related genes such as agrC, atlA, and sarA, as well as amino acid uptake associated with the metabolism of 3-dehydrocarnitine, kynurenine, L-leucine, L-lysine and sebacic acid were inhibited. This study provides evidence for the treatment of MRSA and its biofilms with LNZ combined with RYN. |
| first_indexed | 2024-12-22T20:24:00Z |
| format | Article |
| id | doaj.art-019943277ca04aff9fb1128a77b9765b |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-22T20:24:00Z |
| publishDate | 2022-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-019943277ca04aff9fb1128a77b9765b2022-12-21T18:13:46ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-01-011210.3389/fphar.2021.766309766309The Inhibition Effect of Linezolid With Reyanning Mixture on MRSA and its Biofilm is More Significant than That of Linezolid AloneLulu Zhang0Lulu Zhang1Weifeng Yang2Yajun Chu3Bo Wen4Yungchi Cheng5Tariq Mahmood6Mei Bao7Mei Bao8Feng Ge9Li Li10Jianfeng Yi11Chengqiang Du12Cheng Lu13Yong Tan14Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, ChinaKey Laboratory for Research on Active Ingredients in Natural Medicine of Jiangxi Province, Yichun University, Yichun, ChinaExperimental Research Center, China Academy of Chinese Medical Sciences, Beijing, ChinaTsing Hua De Ren Xi an Happiness Pharmaceutical Co., Ltd., Xi’an, ChinaInstitute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, ChinaDepartment of Pharmacology, Yale University School of Medicine, New Haven, CT, United StatesDepartment of Plant Sciences, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, PakistanInstitute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, ChinaKey Laboratory for Research on Active Ingredients in Natural Medicine of Jiangxi Province, Yichun University, Yichun, ChinaFaculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, ChinaInstitute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, ChinaKey Laboratory for Research on Active Ingredients in Natural Medicine of Jiangxi Province, Yichun University, Yichun, ChinaTsing Hua De Ren Xi an Happiness Pharmaceutical Co., Ltd., Xi’an, ChinaInstitute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, ChinaInstitute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, ChinaMethicillin-resistant Staphylococcus aureus (MRSA) is a superbacterium, and when it forms biofilms, it is difficult to treat even with the first-line of antibiotic linezolid (LNZ). Reyanning mixture (RYN), a compound-based Chinese medicine formula, has been found to have inhibitory effects on biofilms. This study aims to explore the synergistic inhibitory effect and corresponding mechanisms of their (LNZ&RYN) combination on the planktonic as well as biofilm cells of MRSA. Broth microdilution and chessboard methods were employed for the determination of minimum inhibitory concentrations (MICs) and synergistic concentration of LNZ&RYN, respectively. The effect of the combined medication on biofilm and mature biofilm of MRSA were observed by biofilm morphology and permeability experiments, respectively. To unveil the molecular mechanism of action of the synergistic combination of LNZ and RYN, RT-PCR based biofilm-related gene expression analysis and ultra-high pressure liquid chromatography-time-of-flight mass spectrometry based endogenous metabonomic analysis were deployed. The results indicated that 1/16RYN as the best combined dose reduced LNZ (4 μg/ml) to 2 μg/ml. The combined treatment inhibited living MRSA before and after biofilm formation, removed the residual structure of dead bacteria in MRSA biofilms and affected the shape and size of bacteria, resulting in the improvement of biofilm permeability. The mechanism was that biofilm-related genes such as agrC, atlA, and sarA, as well as amino acid uptake associated with the metabolism of 3-dehydrocarnitine, kynurenine, L-leucine, L-lysine and sebacic acid were inhibited. This study provides evidence for the treatment of MRSA and its biofilms with LNZ combined with RYN.https://www.frontiersin.org/articles/10.3389/fphar.2021.766309/fullmethicillin-resistant Staphylococcus aureusbiofilmreyanning mixturelinezolidsynergistic inhibitory effect |
| spellingShingle | Lulu Zhang Lulu Zhang Weifeng Yang Yajun Chu Bo Wen Yungchi Cheng Tariq Mahmood Mei Bao Mei Bao Feng Ge Li Li Jianfeng Yi Chengqiang Du Cheng Lu Yong Tan The Inhibition Effect of Linezolid With Reyanning Mixture on MRSA and its Biofilm is More Significant than That of Linezolid Alone Frontiers in Pharmacology methicillin-resistant Staphylococcus aureus biofilm reyanning mixture linezolid synergistic inhibitory effect |
| title | The Inhibition Effect of Linezolid With Reyanning Mixture on MRSA and its Biofilm is More Significant than That of Linezolid Alone |
| title_full | The Inhibition Effect of Linezolid With Reyanning Mixture on MRSA and its Biofilm is More Significant than That of Linezolid Alone |
| title_fullStr | The Inhibition Effect of Linezolid With Reyanning Mixture on MRSA and its Biofilm is More Significant than That of Linezolid Alone |
| title_full_unstemmed | The Inhibition Effect of Linezolid With Reyanning Mixture on MRSA and its Biofilm is More Significant than That of Linezolid Alone |
| title_short | The Inhibition Effect of Linezolid With Reyanning Mixture on MRSA and its Biofilm is More Significant than That of Linezolid Alone |
| title_sort | inhibition effect of linezolid with reyanning mixture on mrsa and its biofilm is more significant than that of linezolid alone |
| topic | methicillin-resistant Staphylococcus aureus biofilm reyanning mixture linezolid synergistic inhibitory effect |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2021.766309/full |
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