Anthraquinones as Potential Antibiofilm Agents Against Methicillin-Resistant Staphylococcus aureus
Biofilms formed by methicillin-resistant Staphylococcus aureus (MRSA) are one of the contributing factors to recurrent nosocomial infection in humans. There is currently no specific treatment targeting on biofilms in clinical trials approved by FDA, and antibiotics remain the primary therapeutic str...
| Main Authors: | , , , , , , , |
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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 Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2021.709826/full |
| _version_ | 1818590115887316992 |
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| author | Zhi-Man Song Zhi-Man Song Zhi-Man Song Jun-Liang Zhang Kun Zhou Lu-Ming Yue Yu Zhang Chang-Yun Wang Chang-Yun Wang Chang-Yun Wang Kai-Ling Wang Ying Xu |
| author_facet | Zhi-Man Song Zhi-Man Song Zhi-Man Song Jun-Liang Zhang Kun Zhou Lu-Ming Yue Yu Zhang Chang-Yun Wang Chang-Yun Wang Chang-Yun Wang Kai-Ling Wang Ying Xu |
| author_sort | Zhi-Man Song |
| collection | DOAJ |
| description | Biofilms formed by methicillin-resistant Staphylococcus aureus (MRSA) are one of the contributing factors to recurrent nosocomial infection in humans. There is currently no specific treatment targeting on biofilms in clinical trials approved by FDA, and antibiotics remain the primary therapeutic strategy. In this study, two anthraquinone compounds isolated from a rare actinobacterial strain Kitasatospora albolonga R62, 3,8-dihydroxy-l-methylanthraquinon-2-carboxylic acid (1) and 3,6,8-trihydroxy-1-methylanthraquinone-2-carboxylic acid (2), together with their 10 commercial analogs 3–12 were evaluated for antibacterial and antibiofilm activities against MRSA, which led to the discovery of two potential antibiofilm anthraquinone compounds anthraquinone-2-carboxlic acid (6) and rhein (12). The structure-activity relationship analysis of these anthraquinones indicated that the hydroxyl group at the C-2 position of the anthraquinone skeleton played an important role in inhibiting biofilm formation at high concentrations, while the carboxyl group at the same C-2 position had a great influence on the antibacterial activity and biofilm eradication activity. The results of crystal violet and methyl thiazolyl tetrazolium staining assays, as well as scanning electron microscope and confocal scanning laser microscopy imaging of compounds 6 and 12 treatment groups showed that both compounds could disrupt preformed MRSA biofilms possibly by killing or dispersing biofilm cells. RNA-Seq was subsequently used for the preliminary elucidation of the mechanism of biofilm eradication, and the results showed upregulation of phosphate transport-related genes in the overlapping differentially expressed genes of both compound treatment groups. Herein, we propose that anthraquinone compounds 6 and 12 could be considered promising candidates for the development of antibiofilm agents. |
| first_indexed | 2024-12-16T09:51:25Z |
| format | Article |
| id | doaj.art-81d8752238e549ea82fb82079948c80e |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-16T09:51:25Z |
| publishDate | 2021-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-81d8752238e549ea82fb82079948c80e2022-12-21T22:36:03ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2021-09-011210.3389/fmicb.2021.709826709826Anthraquinones as Potential Antibiofilm Agents Against Methicillin-Resistant Staphylococcus aureusZhi-Man Song0Zhi-Man Song1Zhi-Man Song2Jun-Liang Zhang3Kun Zhou4Lu-Ming Yue5Yu Zhang6Chang-Yun Wang7Chang-Yun Wang8Chang-Yun Wang9Kai-Ling Wang10Ying Xu11Shenzhen Key Laboratory of Marine Bioresource and Eco-Environmental Science, Shenzhen Engineering Laboratory for Marine Algal Biotechnology, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, ChinaDepartment of Chemistry, The University of Hong Kong, Pokfulam, Hong Kong, ChinaCollege of Pharmacy, Institute of Materia Medica, Dali University, Dali, ChinaShenzhen Key Laboratory of Marine Bioresource and Eco-Environmental Science, Shenzhen Engineering Laboratory for Marine Algal Biotechnology, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, ChinaShenzhen Key Laboratory of Marine Bioresource and Eco-Environmental Science, Shenzhen Engineering Laboratory for Marine Algal Biotechnology, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, ChinaShenzhen Key Laboratory of Marine Bioresource and Eco-Environmental Science, Shenzhen Engineering Laboratory for Marine Algal Biotechnology, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, ChinaShenzhen Key Laboratory of Marine Bioresource and Eco-Environmental Science, Shenzhen Engineering Laboratory for Marine Algal Biotechnology, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, ChinaKey Laboratory of Marine Drugs, The Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao, ChinaLaboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, Qingdao, ChinaInstitute of Evolution and Marine Biodiversity, Ocean University of China, Qingdao, ChinaCollege of Pharmacy, Institute of Materia Medica, Dali University, Dali, ChinaShenzhen Key Laboratory of Marine Bioresource and Eco-Environmental Science, Shenzhen Engineering Laboratory for Marine Algal Biotechnology, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, ChinaBiofilms formed by methicillin-resistant Staphylococcus aureus (MRSA) are one of the contributing factors to recurrent nosocomial infection in humans. There is currently no specific treatment targeting on biofilms in clinical trials approved by FDA, and antibiotics remain the primary therapeutic strategy. In this study, two anthraquinone compounds isolated from a rare actinobacterial strain Kitasatospora albolonga R62, 3,8-dihydroxy-l-methylanthraquinon-2-carboxylic acid (1) and 3,6,8-trihydroxy-1-methylanthraquinone-2-carboxylic acid (2), together with their 10 commercial analogs 3–12 were evaluated for antibacterial and antibiofilm activities against MRSA, which led to the discovery of two potential antibiofilm anthraquinone compounds anthraquinone-2-carboxlic acid (6) and rhein (12). The structure-activity relationship analysis of these anthraquinones indicated that the hydroxyl group at the C-2 position of the anthraquinone skeleton played an important role in inhibiting biofilm formation at high concentrations, while the carboxyl group at the same C-2 position had a great influence on the antibacterial activity and biofilm eradication activity. The results of crystal violet and methyl thiazolyl tetrazolium staining assays, as well as scanning electron microscope and confocal scanning laser microscopy imaging of compounds 6 and 12 treatment groups showed that both compounds could disrupt preformed MRSA biofilms possibly by killing or dispersing biofilm cells. RNA-Seq was subsequently used for the preliminary elucidation of the mechanism of biofilm eradication, and the results showed upregulation of phosphate transport-related genes in the overlapping differentially expressed genes of both compound treatment groups. Herein, we propose that anthraquinone compounds 6 and 12 could be considered promising candidates for the development of antibiofilm agents.https://www.frontiersin.org/articles/10.3389/fmicb.2021.709826/fullanthraquinonesantibiofilm agentsKitasatospora albolongaRNA-SeqantibioticsPst system |
| spellingShingle | Zhi-Man Song Zhi-Man Song Zhi-Man Song Jun-Liang Zhang Kun Zhou Lu-Ming Yue Yu Zhang Chang-Yun Wang Chang-Yun Wang Chang-Yun Wang Kai-Ling Wang Ying Xu Anthraquinones as Potential Antibiofilm Agents Against Methicillin-Resistant Staphylococcus aureus Frontiers in Microbiology anthraquinones antibiofilm agents Kitasatospora albolonga RNA-Seq antibiotics Pst system |
| title | Anthraquinones as Potential Antibiofilm Agents Against Methicillin-Resistant Staphylococcus aureus |
| title_full | Anthraquinones as Potential Antibiofilm Agents Against Methicillin-Resistant Staphylococcus aureus |
| title_fullStr | Anthraquinones as Potential Antibiofilm Agents Against Methicillin-Resistant Staphylococcus aureus |
| title_full_unstemmed | Anthraquinones as Potential Antibiofilm Agents Against Methicillin-Resistant Staphylococcus aureus |
| title_short | Anthraquinones as Potential Antibiofilm Agents Against Methicillin-Resistant Staphylococcus aureus |
| title_sort | anthraquinones as potential antibiofilm agents against methicillin resistant staphylococcus aureus |
| topic | anthraquinones antibiofilm agents Kitasatospora albolonga RNA-Seq antibiotics Pst system |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2021.709826/full |
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