F0F1-ATPase Contributes to the Fluoride Tolerance and Cariogenicity of Streptococcus mutans
The phenotypic traits of Streptococcus mutans, such as fluoride tolerance, are usually associated with genotypic alterations. The aim of this study was to identify adaptive mutations of S. mutans to gradient fluoride concentrations and possible relationships between the mutations and fluoride tolera...
| 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.2021.777504/full |
| _version_ | 1798024752394141696 |
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| author | Cheng Li Cheng Li Cai Qi Cai Qi Sirui Yang Sirui Yang Zhengyi Li Biao Ren Jiyao Li Jiyao Li Xuedong Zhou Xuedong Zhou Huawei Cai Xin Xu Xin Xu Xian Peng |
| author_facet | Cheng Li Cheng Li Cai Qi Cai Qi Sirui Yang Sirui Yang Zhengyi Li Biao Ren Jiyao Li Jiyao Li Xuedong Zhou Xuedong Zhou Huawei Cai Xin Xu Xin Xu Xian Peng |
| author_sort | Cheng Li |
| collection | DOAJ |
| description | The phenotypic traits of Streptococcus mutans, such as fluoride tolerance, are usually associated with genotypic alterations. The aim of this study was to identify adaptive mutations of S. mutans to gradient fluoride concentrations and possible relationships between the mutations and fluoride tolerance. We identified a highly resistant S. mutans strain (FR1000) with a novel single nucleotide polymorphism (SNP, −36G→T) in the promoter region of F0F1-ATPase gene cluster (SMU_1527-SMU_1534) resistant to 1,000 ppm fluoride using the whole-genome Illumina PE250 sequencing. Thus, a −36G→T F0F1-ATPase promoter mutation from the parental strain S. mutans UA159 was constructed and named UA159-T. qRT-PCR showed that the F0F1-ATPase gene expression of both FR1000 and UA159-T was up-regulated, and fluoride tolerance of UA159-T was significantly improved. Complementation of Dicyclohexylcarbodiimide (DCCD), a specific inhibitor of F0F1-ATPase, increased fluoride susceptibility of FR1000 and UA159-T. Intracellular fluoride concentrations of fluoride tolerance strains were higher compared to UA159 strain as demonstrated by 18F analysis. Further validation with rat caries models showed that UA159-T caused more severe caries lesions under fluoride exposure compared with its parental UA159 strain. Overall, the identified −36G→T mutation in the promoter region of F0F1-ATPase gene drastically contributed to the fluoride tolerance and enhanced cariogenicity of S. mutans. These findings provided new insights into the mechanism of microbial fluoride tolerance, and suggested F0F1-ATPase as a potential target for suppressing fluoride resistant strains. |
| first_indexed | 2024-04-11T18:07:41Z |
| format | Article |
| id | doaj.art-8cfb3ed1b73940ce9cfc354bece220d6 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-04-11T18:07:41Z |
| publishDate | 2022-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-8cfb3ed1b73940ce9cfc354bece220d62022-12-22T04:10:16ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2022-01-011210.3389/fmicb.2021.777504777504F0F1-ATPase Contributes to the Fluoride Tolerance and Cariogenicity of Streptococcus mutansCheng Li0Cheng Li1Cai Qi2Cai Qi3Sirui Yang4Sirui Yang5Zhengyi Li6Biao Ren7Jiyao Li8Jiyao Li9Xuedong Zhou10Xuedong Zhou11Huawei Cai12Xin Xu13Xin Xu14Xian Peng15State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, ChinaDepartment of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, ChinaState Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, ChinaDepartment of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, ChinaState Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, ChinaDepartment of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, ChinaState Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, ChinaState Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, ChinaState Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, ChinaDepartment of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, ChinaState Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, ChinaDepartment of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, ChinaLaboratory of Nuclear Medicine, Department of Clinical Nuclear Medicine, West China Hospital, Sichuan University, Chengdu, ChinaState Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, ChinaDepartment of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, ChinaState Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, ChinaThe phenotypic traits of Streptococcus mutans, such as fluoride tolerance, are usually associated with genotypic alterations. The aim of this study was to identify adaptive mutations of S. mutans to gradient fluoride concentrations and possible relationships between the mutations and fluoride tolerance. We identified a highly resistant S. mutans strain (FR1000) with a novel single nucleotide polymorphism (SNP, −36G→T) in the promoter region of F0F1-ATPase gene cluster (SMU_1527-SMU_1534) resistant to 1,000 ppm fluoride using the whole-genome Illumina PE250 sequencing. Thus, a −36G→T F0F1-ATPase promoter mutation from the parental strain S. mutans UA159 was constructed and named UA159-T. qRT-PCR showed that the F0F1-ATPase gene expression of both FR1000 and UA159-T was up-regulated, and fluoride tolerance of UA159-T was significantly improved. Complementation of Dicyclohexylcarbodiimide (DCCD), a specific inhibitor of F0F1-ATPase, increased fluoride susceptibility of FR1000 and UA159-T. Intracellular fluoride concentrations of fluoride tolerance strains were higher compared to UA159 strain as demonstrated by 18F analysis. Further validation with rat caries models showed that UA159-T caused more severe caries lesions under fluoride exposure compared with its parental UA159 strain. Overall, the identified −36G→T mutation in the promoter region of F0F1-ATPase gene drastically contributed to the fluoride tolerance and enhanced cariogenicity of S. mutans. These findings provided new insights into the mechanism of microbial fluoride tolerance, and suggested F0F1-ATPase as a potential target for suppressing fluoride resistant strains.https://www.frontiersin.org/articles/10.3389/fmicb.2021.777504/fullStreptococcus mutansfluoride(s)genomicscariesantimicrobials |
| spellingShingle | Cheng Li Cheng Li Cai Qi Cai Qi Sirui Yang Sirui Yang Zhengyi Li Biao Ren Jiyao Li Jiyao Li Xuedong Zhou Xuedong Zhou Huawei Cai Xin Xu Xin Xu Xian Peng F0F1-ATPase Contributes to the Fluoride Tolerance and Cariogenicity of Streptococcus mutans Frontiers in Microbiology Streptococcus mutans fluoride(s) genomics caries antimicrobials |
| title | F0F1-ATPase Contributes to the Fluoride Tolerance and Cariogenicity of Streptococcus mutans |
| title_full | F0F1-ATPase Contributes to the Fluoride Tolerance and Cariogenicity of Streptococcus mutans |
| title_fullStr | F0F1-ATPase Contributes to the Fluoride Tolerance and Cariogenicity of Streptococcus mutans |
| title_full_unstemmed | F0F1-ATPase Contributes to the Fluoride Tolerance and Cariogenicity of Streptococcus mutans |
| title_short | F0F1-ATPase Contributes to the Fluoride Tolerance and Cariogenicity of Streptococcus mutans |
| title_sort | f0f1 atpase contributes to the fluoride tolerance and cariogenicity of streptococcus mutans |
| topic | Streptococcus mutans fluoride(s) genomics caries antimicrobials |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2021.777504/full |
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