Investigation of drug resistance of caries-related streptococci to antimicrobial peptide GH12
Dental caries is associated with caries-related streptococci and antimicrobial agents have been widely used for caries control, but troubled by antibiotic resistance. This study aimed to investigate the intrinsic and acquired resistance of caries-related streptococci to antimicrobial peptide GH12, w...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-09-01
|
| Series: | Frontiers in Cellular and Infection Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2022.991938/full |
| _version_ | 1818480293942657024 |
|---|---|
| author | Xinwei Li Xinwei Li Yufei Wang Xuelian Jiang Yuhao Zeng Xinran Zhao Jumpei Washio Nobuhiro Takahashi Linglin Zhang |
| author_facet | Xinwei Li Xinwei Li Yufei Wang Xuelian Jiang Yuhao Zeng Xinran Zhao Jumpei Washio Nobuhiro Takahashi Linglin Zhang |
| author_sort | Xinwei Li |
| collection | DOAJ |
| description | Dental caries is associated with caries-related streptococci and antimicrobial agents have been widely used for caries control, but troubled by antibiotic resistance. This study aimed to investigate the intrinsic and acquired resistance of caries-related streptococci to antimicrobial peptide GH12, which was proven promising for caries control, and preliminarily explore the phenotypic changes and whole genome of stable acquired resistant strains. In this study, susceptibility assays and resistance assays were performed, followed by stability assays of resistance, to evaluate the intrinsic resistance and the potential resistance of caries-related streptococci. Then, the phenotypic changes of the stable acquired resistant strain were explored. The whole genome of the resistant strain was sequenced and analyzed by second-generation and third-generation high-throughput sequencing technologies. Streptococcus gordonii and Streptococcus sanguinis were intrinsically resistant to GH12 compared to cariogenic Streptococcus mutans. Acquired GH12 resistance in one S. sanguinis and four S. mutans clinical strains was transient but stable in one S. mutans strain (COCC33-14). However, acquired resistance to daptomycin (DAP) and chlorhexidine in all strains was stable. Furthermore, the COCC33-14 showed cross-resistance to DAP and delayed growth rates and a lower population. However, no drug-resistant gene mutation was detected in this strain, but 6 new and 5 missing genes were found. Among them, annotation of one new gene (gene 1782|COCC33-14R) is related to the integral component of the membrane, and one missing gene rpsN is associated with the metabolism and growth of bacteria. The results indicate that stable resistant mutants of caries-related streptococci could hardly be selected by exposure to consecutive sublethal GH12, but the risk still existed. Resistance in COCC33-14R is mainly related to changes in the cell envelope. |
| first_indexed | 2024-12-10T11:21:34Z |
| format | Article |
| id | doaj.art-70f97032821e4691ab04eb75778d8896 |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-12-10T11:21:34Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-70f97032821e4691ab04eb75778d88962022-12-22T01:50:55ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882022-09-011210.3389/fcimb.2022.991938991938Investigation of drug resistance of caries-related streptococci to antimicrobial peptide GH12Xinwei Li0Xinwei Li1Yufei Wang2Xuelian Jiang3Yuhao Zeng4Xinran Zhao5Jumpei Washio6Nobuhiro Takahashi7Linglin Zhang8State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu, ChinaDepartment of Stomatology, Chengdu Second People’s Hospital, Chengdu, ChinaState Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu, ChinaState Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu, ChinaState Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu, ChinaState Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu, ChinaDivision of Oral Ecology and Biochemistry, Graduate School of Dentistry, Tohoku University, Sendai, JapanDivision of Oral Ecology and Biochemistry, Graduate School of Dentistry, Tohoku University, Sendai, JapanState Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu, ChinaDental caries is associated with caries-related streptococci and antimicrobial agents have been widely used for caries control, but troubled by antibiotic resistance. This study aimed to investigate the intrinsic and acquired resistance of caries-related streptococci to antimicrobial peptide GH12, which was proven promising for caries control, and preliminarily explore the phenotypic changes and whole genome of stable acquired resistant strains. In this study, susceptibility assays and resistance assays were performed, followed by stability assays of resistance, to evaluate the intrinsic resistance and the potential resistance of caries-related streptococci. Then, the phenotypic changes of the stable acquired resistant strain were explored. The whole genome of the resistant strain was sequenced and analyzed by second-generation and third-generation high-throughput sequencing technologies. Streptococcus gordonii and Streptococcus sanguinis were intrinsically resistant to GH12 compared to cariogenic Streptococcus mutans. Acquired GH12 resistance in one S. sanguinis and four S. mutans clinical strains was transient but stable in one S. mutans strain (COCC33-14). However, acquired resistance to daptomycin (DAP) and chlorhexidine in all strains was stable. Furthermore, the COCC33-14 showed cross-resistance to DAP and delayed growth rates and a lower population. However, no drug-resistant gene mutation was detected in this strain, but 6 new and 5 missing genes were found. Among them, annotation of one new gene (gene 1782|COCC33-14R) is related to the integral component of the membrane, and one missing gene rpsN is associated with the metabolism and growth of bacteria. The results indicate that stable resistant mutants of caries-related streptococci could hardly be selected by exposure to consecutive sublethal GH12, but the risk still existed. Resistance in COCC33-14R is mainly related to changes in the cell envelope.https://www.frontiersin.org/articles/10.3389/fcimb.2022.991938/fullantimicrobial peptidedrug resistancedental cariesstreptococciwhole genome sequencing |
| spellingShingle | Xinwei Li Xinwei Li Yufei Wang Xuelian Jiang Yuhao Zeng Xinran Zhao Jumpei Washio Nobuhiro Takahashi Linglin Zhang Investigation of drug resistance of caries-related streptococci to antimicrobial peptide GH12 Frontiers in Cellular and Infection Microbiology antimicrobial peptide drug resistance dental caries streptococci whole genome sequencing |
| title | Investigation of drug resistance of caries-related streptococci to antimicrobial peptide GH12 |
| title_full | Investigation of drug resistance of caries-related streptococci to antimicrobial peptide GH12 |
| title_fullStr | Investigation of drug resistance of caries-related streptococci to antimicrobial peptide GH12 |
| title_full_unstemmed | Investigation of drug resistance of caries-related streptococci to antimicrobial peptide GH12 |
| title_short | Investigation of drug resistance of caries-related streptococci to antimicrobial peptide GH12 |
| title_sort | investigation of drug resistance of caries related streptococci to antimicrobial peptide gh12 |
| topic | antimicrobial peptide drug resistance dental caries streptococci whole genome sequencing |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2022.991938/full |
| work_keys_str_mv | AT xinweili investigationofdrugresistanceofcariesrelatedstreptococcitoantimicrobialpeptidegh12 AT xinweili investigationofdrugresistanceofcariesrelatedstreptococcitoantimicrobialpeptidegh12 AT yufeiwang investigationofdrugresistanceofcariesrelatedstreptococcitoantimicrobialpeptidegh12 AT xuelianjiang investigationofdrugresistanceofcariesrelatedstreptococcitoantimicrobialpeptidegh12 AT yuhaozeng investigationofdrugresistanceofcariesrelatedstreptococcitoantimicrobialpeptidegh12 AT xinranzhao investigationofdrugresistanceofcariesrelatedstreptococcitoantimicrobialpeptidegh12 AT jumpeiwashio investigationofdrugresistanceofcariesrelatedstreptococcitoantimicrobialpeptidegh12 AT nobuhirotakahashi investigationofdrugresistanceofcariesrelatedstreptococcitoantimicrobialpeptidegh12 AT linglinzhang investigationofdrugresistanceofcariesrelatedstreptococcitoantimicrobialpeptidegh12 |