Inhibition of Streptococcus mutans adhesion and biofilm formation with small-molecule inhibitors of sortase A from Juniperus chinensis
Background Streptococcus mutans, an important Gram-positive pathogen in dental caries, uses sortase A (SrtA) to anchor surface proteins to the bacterial cell wall, thereby promoting biofilm formation and attachment to the tooth surface.Design Based on activity-guided separation, inhibitors of S. mut...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-12-01
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| Series: | Journal of Oral Microbiology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/20002297.2022.2088937 |
| _version_ | 1818204176393437184 |
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| author | Eunji Cho Ji-Yeon Hwang Jae Sung Park Daehyun Oh Dong-Chan Oh Hyeung-Geun Park Jongheon Shin Ki-Bong Oh |
| author_facet | Eunji Cho Ji-Yeon Hwang Jae Sung Park Daehyun Oh Dong-Chan Oh Hyeung-Geun Park Jongheon Shin Ki-Bong Oh |
| author_sort | Eunji Cho |
| collection | DOAJ |
| description | Background Streptococcus mutans, an important Gram-positive pathogen in dental caries, uses sortase A (SrtA) to anchor surface proteins to the bacterial cell wall, thereby promoting biofilm formation and attachment to the tooth surface.Design Based on activity-guided separation, inhibitors of S. mutans SrtA were isolated from Juniperus chinensis and identified through combined spectroscopic analysis. Further effects of isolated SrtA inhibitor on S. mutans were evaluated on bacterial aggregation, adherence and biofilm formation.Results Six compounds (1–6) were isolated from the dried heartwood of J. chinensis. A novel compound designated 3’,3”-dihydroxy-(−)-matairesinol (1) was identified, which exhibited potent inhibitory activity toward S. mutans SrtA (IC50 = 16.1 μM) without affecting microbial viability (minimum inhibitory concentration > 300 μM). The results of subsequent bioassays using compound 1 indicated that this compound inhibits S. mutans aggregation, adhesion and biofilm formation on solid surfaces by inhibiting SrtA activity. The onset and magnitude of inhibition of adherence and biofilm formation in S. mutans treated with compound 1 at 4× the SrtA IC50 are comparable to the behaviors of the untreated srtA-deletion mutant.Conclusion Our findings suggest that small-molecule inhibitors of S. mutans SrtA may be useful for the prevention of dental plaque and treatment of dental microbial diseases. |
| first_indexed | 2024-12-12T03:37:04Z |
| format | Article |
| id | doaj.art-9468c62f7b8241ce9adf221971a4b7bc |
| institution | Directory Open Access Journal |
| issn | 2000-2297 |
| language | English |
| last_indexed | 2024-12-12T03:37:04Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Oral Microbiology |
| spelling | doaj.art-9468c62f7b8241ce9adf221971a4b7bc2022-12-22T00:39:46ZengTaylor & Francis GroupJournal of Oral Microbiology2000-22972022-12-0114110.1080/20002297.2022.2088937Inhibition of Streptococcus mutans adhesion and biofilm formation with small-molecule inhibitors of sortase A from Juniperus chinensisEunji Cho0Ji-Yeon Hwang1Jae Sung Park2Daehyun Oh3Dong-Chan Oh4Hyeung-Geun Park5Jongheon Shin6Ki-Bong Oh7Department of Agricultural Biotechnology, College of Agriculture and Life Sciences, Seoul National University, Seoul, Republic of KoreaNatural Products Research Institute, College of Pharmacy, Seoul National University, Seoul, Republic of KoreaNatural Products Research Institute, College of Pharmacy, Seoul National University, Seoul, Republic of KoreaResearch Institute of Pharmaceutical Sciences and College of Pharmacy, Seoul National University, Seoul, Republic of KoreaNatural Products Research Institute, College of Pharmacy, Seoul National University, Seoul, Republic of KoreaResearch Institute of Pharmaceutical Sciences and College of Pharmacy, Seoul National University, Seoul, Republic of KoreaNatural Products Research Institute, College of Pharmacy, Seoul National University, Seoul, Republic of KoreaDepartment of Agricultural Biotechnology, College of Agriculture and Life Sciences, Seoul National University, Seoul, Republic of KoreaBackground Streptococcus mutans, an important Gram-positive pathogen in dental caries, uses sortase A (SrtA) to anchor surface proteins to the bacterial cell wall, thereby promoting biofilm formation and attachment to the tooth surface.Design Based on activity-guided separation, inhibitors of S. mutans SrtA were isolated from Juniperus chinensis and identified through combined spectroscopic analysis. Further effects of isolated SrtA inhibitor on S. mutans were evaluated on bacterial aggregation, adherence and biofilm formation.Results Six compounds (1–6) were isolated from the dried heartwood of J. chinensis. A novel compound designated 3’,3”-dihydroxy-(−)-matairesinol (1) was identified, which exhibited potent inhibitory activity toward S. mutans SrtA (IC50 = 16.1 μM) without affecting microbial viability (minimum inhibitory concentration > 300 μM). The results of subsequent bioassays using compound 1 indicated that this compound inhibits S. mutans aggregation, adhesion and biofilm formation on solid surfaces by inhibiting SrtA activity. The onset and magnitude of inhibition of adherence and biofilm formation in S. mutans treated with compound 1 at 4× the SrtA IC50 are comparable to the behaviors of the untreated srtA-deletion mutant.Conclusion Our findings suggest that small-molecule inhibitors of S. mutans SrtA may be useful for the prevention of dental plaque and treatment of dental microbial diseases.https://www.tandfonline.com/doi/10.1080/20002297.2022.2088937Adhesionbiofilm formationJuniperus chinensissortase A inhibitorStreptococcus mutans |
| spellingShingle | Eunji Cho Ji-Yeon Hwang Jae Sung Park Daehyun Oh Dong-Chan Oh Hyeung-Geun Park Jongheon Shin Ki-Bong Oh Inhibition of Streptococcus mutans adhesion and biofilm formation with small-molecule inhibitors of sortase A from Juniperus chinensis Journal of Oral Microbiology Adhesion biofilm formation Juniperus chinensis sortase A inhibitor Streptococcus mutans |
| title | Inhibition of Streptococcus mutans adhesion and biofilm formation with small-molecule inhibitors of sortase A from Juniperus chinensis |
| title_full | Inhibition of Streptococcus mutans adhesion and biofilm formation with small-molecule inhibitors of sortase A from Juniperus chinensis |
| title_fullStr | Inhibition of Streptococcus mutans adhesion and biofilm formation with small-molecule inhibitors of sortase A from Juniperus chinensis |
| title_full_unstemmed | Inhibition of Streptococcus mutans adhesion and biofilm formation with small-molecule inhibitors of sortase A from Juniperus chinensis |
| title_short | Inhibition of Streptococcus mutans adhesion and biofilm formation with small-molecule inhibitors of sortase A from Juniperus chinensis |
| title_sort | inhibition of streptococcus mutans adhesion and biofilm formation with small molecule inhibitors of sortase a from juniperus chinensis |
| topic | Adhesion biofilm formation Juniperus chinensis sortase A inhibitor Streptococcus mutans |
| url | https://www.tandfonline.com/doi/10.1080/20002297.2022.2088937 |
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