Small-Molecule Compound SYG-180-2-2 to Effectively Prevent the Biofilm Formation of Methicillin-Resistant Staphylococcus aureus
The resistance of methicillin-resistant Staphylococcus aureus (MRSA) has augmented due to the abuse of antibiotics, bringing about difficulties in the treatment of infection especially with the formation of biofilm. Thus, it is essential to develop antimicrobials. Here we synthesized a novel small-m...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-01-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2021.770657/full |
| _version_ | 1818965893625937920 |
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| author | Lulin Rao Yaoguang Sheng Jiao Zhang Yanlei Xu Jingyi Yu Bingjie Wang Huilin Zhao Xinyi Wang Yinjuan Guo Xiaocui Wu Zengqiang Song Fangyou Yu Fangyou Yu Lingling Zhan |
| author_facet | Lulin Rao Yaoguang Sheng Jiao Zhang Yanlei Xu Jingyi Yu Bingjie Wang Huilin Zhao Xinyi Wang Yinjuan Guo Xiaocui Wu Zengqiang Song Fangyou Yu Fangyou Yu Lingling Zhan |
| author_sort | Lulin Rao |
| collection | DOAJ |
| description | The resistance of methicillin-resistant Staphylococcus aureus (MRSA) has augmented due to the abuse of antibiotics, bringing about difficulties in the treatment of infection especially with the formation of biofilm. Thus, it is essential to develop antimicrobials. Here we synthesized a novel small-molecule compound, which we termed SYG-180-2-2 (C21H16N2OSe), that had antibiofilm activity. The aim of this study was to demonstrate the antibiofilm effect of SYG-180-2-2 against clinical MRSA isolates at a subinhibitory concentration (4 μg/ml). In this study, it was showed that significant suppression in biofilm formation occurred with SYG-180-2-2 treatment, the inhibition ranged between 65.0 and 85.2%. Subsequently, confocal laser scanning microscopy and a bacterial biofilm metabolism activity assay further demonstrated that SYG-180-2-2 could suppress biofilm. Additionally, SYG-180-2-2 reduced bacterial adhesion and polysaccharide intercellular adhesin (PIA) production. It was found that the expression of icaA and other biofilm-related genes were downregulated as evaluated by RT-qPCR. At the same time, icaR and codY were upregulated when biofilms were treated with SYG-180-2-2. Based on the above results, we speculate that SYG-180-2-2 inhibits the formation of biofilm by affecting cell adhesion and the expression of genes related to PIA production. Above all, SYG-180-2-2 had no toxic effects on human normal alveolar epithelial cells BEAS-2B. Collectively, the small-molecule compound SYG-180-2-2 is a safe and effective antibacterial agent for inhibiting MRSA biofilm. |
| first_indexed | 2024-12-20T13:24:15Z |
| format | Article |
| id | doaj.art-d9d23a5fb23c4b148dbfb0302acf4b77 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-20T13:24:15Z |
| publishDate | 2022-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-d9d23a5fb23c4b148dbfb0302acf4b772022-12-21T19:39:18ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2022-01-011210.3389/fmicb.2021.770657770657Small-Molecule Compound SYG-180-2-2 to Effectively Prevent the Biofilm Formation of Methicillin-Resistant Staphylococcus aureusLulin Rao0Yaoguang Sheng1Jiao Zhang2Yanlei Xu3Jingyi Yu4Bingjie Wang5Huilin Zhao6Xinyi Wang7Yinjuan Guo8Xiaocui Wu9Zengqiang Song10Fangyou Yu11Fangyou Yu12Lingling Zhan13Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaSchool of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, ChinaDepartment of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaJiangxi Provincial Key Laboratory of Preventive Medicine, School of Public Health, Nanchang University, Nanchang, ChinaDepartment of Clinical Laboratory, School of Medicine, Shanghai Pulmonary Hospital, Tongji University, Shanghai, ChinaDepartment of Clinical Laboratory, School of Medicine, Shanghai Pulmonary Hospital, Tongji University, Shanghai, ChinaDepartment of Clinical Laboratory, School of Medicine, Shanghai Pulmonary Hospital, Tongji University, Shanghai, ChinaDepartment of Clinical Laboratory, School of Medicine, Shanghai Pulmonary Hospital, Tongji University, Shanghai, ChinaDepartment of Clinical Laboratory, School of Medicine, Shanghai Pulmonary Hospital, Tongji University, Shanghai, ChinaDepartment of Clinical Laboratory, School of Medicine, Shanghai Pulmonary Hospital, Tongji University, Shanghai, ChinaSchool of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, ChinaDepartment of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Clinical Laboratory, School of Medicine, Shanghai Pulmonary Hospital, Tongji University, Shanghai, ChinaDepartment of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaThe resistance of methicillin-resistant Staphylococcus aureus (MRSA) has augmented due to the abuse of antibiotics, bringing about difficulties in the treatment of infection especially with the formation of biofilm. Thus, it is essential to develop antimicrobials. Here we synthesized a novel small-molecule compound, which we termed SYG-180-2-2 (C21H16N2OSe), that had antibiofilm activity. The aim of this study was to demonstrate the antibiofilm effect of SYG-180-2-2 against clinical MRSA isolates at a subinhibitory concentration (4 μg/ml). In this study, it was showed that significant suppression in biofilm formation occurred with SYG-180-2-2 treatment, the inhibition ranged between 65.0 and 85.2%. Subsequently, confocal laser scanning microscopy and a bacterial biofilm metabolism activity assay further demonstrated that SYG-180-2-2 could suppress biofilm. Additionally, SYG-180-2-2 reduced bacterial adhesion and polysaccharide intercellular adhesin (PIA) production. It was found that the expression of icaA and other biofilm-related genes were downregulated as evaluated by RT-qPCR. At the same time, icaR and codY were upregulated when biofilms were treated with SYG-180-2-2. Based on the above results, we speculate that SYG-180-2-2 inhibits the formation of biofilm by affecting cell adhesion and the expression of genes related to PIA production. Above all, SYG-180-2-2 had no toxic effects on human normal alveolar epithelial cells BEAS-2B. Collectively, the small-molecule compound SYG-180-2-2 is a safe and effective antibacterial agent for inhibiting MRSA biofilm.https://www.frontiersin.org/articles/10.3389/fmicb.2021.770657/fullMRSASYG-180-2-2biofilmcell adhesionicaA |
| spellingShingle | Lulin Rao Yaoguang Sheng Jiao Zhang Yanlei Xu Jingyi Yu Bingjie Wang Huilin Zhao Xinyi Wang Yinjuan Guo Xiaocui Wu Zengqiang Song Fangyou Yu Fangyou Yu Lingling Zhan Small-Molecule Compound SYG-180-2-2 to Effectively Prevent the Biofilm Formation of Methicillin-Resistant Staphylococcus aureus Frontiers in Microbiology MRSA SYG-180-2-2 biofilm cell adhesion icaA |
| title | Small-Molecule Compound SYG-180-2-2 to Effectively Prevent the Biofilm Formation of Methicillin-Resistant Staphylococcus aureus |
| title_full | Small-Molecule Compound SYG-180-2-2 to Effectively Prevent the Biofilm Formation of Methicillin-Resistant Staphylococcus aureus |
| title_fullStr | Small-Molecule Compound SYG-180-2-2 to Effectively Prevent the Biofilm Formation of Methicillin-Resistant Staphylococcus aureus |
| title_full_unstemmed | Small-Molecule Compound SYG-180-2-2 to Effectively Prevent the Biofilm Formation of Methicillin-Resistant Staphylococcus aureus |
| title_short | Small-Molecule Compound SYG-180-2-2 to Effectively Prevent the Biofilm Formation of Methicillin-Resistant Staphylococcus aureus |
| title_sort | small molecule compound syg 180 2 2 to effectively prevent the biofilm formation of methicillin resistant staphylococcus aureus |
| topic | MRSA SYG-180-2-2 biofilm cell adhesion icaA |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2021.770657/full |
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