Andrographolide Sulfonate Is a Promising Treatment to Combat Methicillin-resistant Staphylococcus aureus and Its Biofilms
Methicillin-resistant Staphylococcus aureus (MRSA) is a drug-resistant pathogen threatening human health and safety. Biofilms are an important cause of its drug resistance and pathogenicity. Inhibition and elimination of biofilms is an important strategy for the treatment of MRSA infection. Androgra...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-09-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.720685/full |
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| author | Lulu Zhang Lulu Zhang Bo Wen Mei Bao Mei Bao Yungchi Cheng Tariq Mahmood Weifeng Yang Qing Chen Qing Chen Lang Lv Li Li Jianfeng Yi Ning Xie Cheng Lu Yong Tan |
| author_facet | Lulu Zhang Lulu Zhang Bo Wen Mei Bao Mei Bao Yungchi Cheng Tariq Mahmood Weifeng Yang Qing Chen Qing Chen Lang Lv Li Li Jianfeng Yi Ning Xie Cheng Lu Yong Tan |
| author_sort | Lulu Zhang |
| collection | DOAJ |
| description | Methicillin-resistant Staphylococcus aureus (MRSA) is a drug-resistant pathogen threatening human health and safety. Biofilms are an important cause of its drug resistance and pathogenicity. Inhibition and elimination of biofilms is an important strategy for the treatment of MRSA infection. Andrographolide sulfonate (AS) is an active component of the traditional herbal medicine Andrographis paniculata. This study aims to explore the inhibitory effect and corresponding mechanisms of AS on MRSA and its biofilms. Three doses of AS (6.25, 12.5, and 25 mg/ml) were introduced to MRSA with biofilms. In vitro antibacterial testing and morphological observation were used to confirm the inhibitory effect of AS on MRSA with biofilms. Real-time PCR and metabonomics were used to explore the underlying mechanisms of the effect by studying the expression of biofilm-related genes and endogenous metabolites. AS displayed significant anti-MRSA activity, and its minimum inhibitory concentration was 50 μg/ml. Also, AS inhibited biofilms and improved biofilm permeability. The mechanisms are mediated by the inhibition of the expression of genes, such as quorum sensing system regulatory genes (agrD and sarA), microbial surface components–recognizing adhesion matrix genes (clfA and fnbB), intercellular adhesion genes (icaA, icaD, and PIA), and a gene related to cellular eDNA release (cidA), and the downregulation of five biofilm-related metabolites, including anthranilic acid, D-lactic acid, kynurenine, L-homocitrulline, and sebacic acid. This study provided valuable evidence for the activity of AS against MRSA and its biofilms and extended the methods to combat MRSA infection. |
| first_indexed | 2024-12-22T09:37:19Z |
| format | Article |
| id | doaj.art-fe4fca6e28e74d1db0c42a34a088a4c9 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-22T09:37:19Z |
| publishDate | 2021-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-fe4fca6e28e74d1db0c42a34a088a4c92022-12-21T18:30:48ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-09-011210.3389/fphar.2021.720685720685Andrographolide Sulfonate Is a Promising Treatment to Combat Methicillin-resistant Staphylococcus aureus and Its BiofilmsLulu Zhang0Lulu Zhang1Bo Wen2Mei Bao3Mei Bao4Yungchi Cheng5Tariq Mahmood6Weifeng Yang7Qing Chen8Qing Chen9Lang Lv10Li Li11Jianfeng Yi12Ning Xie13Cheng Lu14Yong Tan15Institute 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, 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, ChinaKey Laboratory for Research on Active Ingredients in Natural Medicine of Jiangxi Province, Yichun University, Yichun, 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, PakistanMedical Experimental Center, China Academy of Chinese Medical Sciences, Beijing, 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, ChinaQingfeng Pharmaceutical Co. Ltd., Ganzhou, 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, ChinaQingfeng Pharmaceutical Co. Ltd., Ganzhou, 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 drug-resistant pathogen threatening human health and safety. Biofilms are an important cause of its drug resistance and pathogenicity. Inhibition and elimination of biofilms is an important strategy for the treatment of MRSA infection. Andrographolide sulfonate (AS) is an active component of the traditional herbal medicine Andrographis paniculata. This study aims to explore the inhibitory effect and corresponding mechanisms of AS on MRSA and its biofilms. Three doses of AS (6.25, 12.5, and 25 mg/ml) were introduced to MRSA with biofilms. In vitro antibacterial testing and morphological observation were used to confirm the inhibitory effect of AS on MRSA with biofilms. Real-time PCR and metabonomics were used to explore the underlying mechanisms of the effect by studying the expression of biofilm-related genes and endogenous metabolites. AS displayed significant anti-MRSA activity, and its minimum inhibitory concentration was 50 μg/ml. Also, AS inhibited biofilms and improved biofilm permeability. The mechanisms are mediated by the inhibition of the expression of genes, such as quorum sensing system regulatory genes (agrD and sarA), microbial surface components–recognizing adhesion matrix genes (clfA and fnbB), intercellular adhesion genes (icaA, icaD, and PIA), and a gene related to cellular eDNA release (cidA), and the downregulation of five biofilm-related metabolites, including anthranilic acid, D-lactic acid, kynurenine, L-homocitrulline, and sebacic acid. This study provided valuable evidence for the activity of AS against MRSA and its biofilms and extended the methods to combat MRSA infection.https://www.frontiersin.org/articles/10.3389/fphar.2021.720685/fullandrographolide sulfonatemethicillin-resistant Staphylococcus aureusdrug-resistant biofilmRT-PCRmetabonomics |
| spellingShingle | Lulu Zhang Lulu Zhang Bo Wen Mei Bao Mei Bao Yungchi Cheng Tariq Mahmood Weifeng Yang Qing Chen Qing Chen Lang Lv Li Li Jianfeng Yi Ning Xie Cheng Lu Yong Tan Andrographolide Sulfonate Is a Promising Treatment to Combat Methicillin-resistant Staphylococcus aureus and Its Biofilms Frontiers in Pharmacology andrographolide sulfonate methicillin-resistant Staphylococcus aureus drug-resistant biofilm RT-PCR metabonomics |
| title | Andrographolide Sulfonate Is a Promising Treatment to Combat Methicillin-resistant Staphylococcus aureus and Its Biofilms |
| title_full | Andrographolide Sulfonate Is a Promising Treatment to Combat Methicillin-resistant Staphylococcus aureus and Its Biofilms |
| title_fullStr | Andrographolide Sulfonate Is a Promising Treatment to Combat Methicillin-resistant Staphylococcus aureus and Its Biofilms |
| title_full_unstemmed | Andrographolide Sulfonate Is a Promising Treatment to Combat Methicillin-resistant Staphylococcus aureus and Its Biofilms |
| title_short | Andrographolide Sulfonate Is a Promising Treatment to Combat Methicillin-resistant Staphylococcus aureus and Its Biofilms |
| title_sort | andrographolide sulfonate is a promising treatment to combat methicillin resistant staphylococcus aureus and its biofilms |
| topic | andrographolide sulfonate methicillin-resistant Staphylococcus aureus drug-resistant biofilm RT-PCR metabonomics |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2021.720685/full |
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