Academic Journal
An XRE-type regulator in Streptococcus mutans plays an important role in brpA expression and oxidative stress tolerance response.
| Τίτλος: | An XRE-type regulator in Streptococcus mutans plays an important role in brpA expression and oxidative stress tolerance response. |
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| Συγγραφείς: | Wen ZT; Department of Oral and Craniofacial Biology, School of Dentistry, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA.; Department of Microbiology, Immunology and Parasitology, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA., Ellepola K; Department of Oral and Craniofacial Biology, School of Dentistry, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA., Guillot LC; Department of Oral and Craniofacial Biology, School of Dentistry, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA., Dhaked HPS; Department of Oral and Craniofacial Biology, School of Dentistry, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA., Wu H; Department of Integrative Biosciences, School of Dentistry, Oregon Health and Science University, Portland, Oregon, USA. |
| Πηγή: | Microbiology spectrum [Microbiol Spectr] 2026 Sep; Vol. 14 (9), pp. e0011626. Date of Electronic Publication: 2026 Jul 21. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: ASM Press Country of Publication: United States NLM ID: 101634614 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2165-0497 (Electronic) Linking ISSN: 21650497 NLM ISO Abbreviation: Microbiol Spectr Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Washington, DC : ASM Press, 2013- |
| Ιατρικοί όροι (MeSH): | Streptococcus mutans*/genetics , Streptococcus mutans*/metabolism , Bacterial Proteins*/genetics , Bacterial Proteins*/metabolism , Oxidative Stress*, Hydrogen Peroxide/pharmacology ; Biofilms/growth & development ; Gene Expression Regulation, Bacterial ; Promoter Regions, Genetic ; Response Elements |
| Περίληψη: | This study used a functional genomics approach to explore the role of a xenobiotic response element (XRE)-type regulator (SMU.405c) in Streptococcus mutans physiology, including the expression of biofilm regulatory protein BrpA. Results showed that deletional mutation of xre significantly reduced the ability of the deficient mutant to grow in the presence of methyl viologen, a commonly used oxidative stressor (P < 0.001). When challenged in a hydrogen peroxide killing assay, the survival rate of the ∆xre mutant was >2-log less than the parent strain after 60 min (P < 0.001). Luciferase reporter fusion assays showed that xre deficiency had no significant effect on luciferase expression when it was under the control of the intact brpA promoter, but the reporter activity increased by >6-fold (P < 0.001) when the reporter gene was fused to a brpA promoter derivative with deletion of a putative XRE-binding box. Electrophoretic mobility shift assay (EMSA) showed that recombinant XRE interacted with the brpA promoter, resulting in an electrophoretic shift of the promoter probes. In vitro transcription assay also showed that inclusion of XRE caused transcription to fall off, significantly reducing full-length brpA transcripts. RNA-seq analysis revealed that deficiency of XRE led to altered expression of >102 genes by >2-fold (P < 0.05), including 28 with increased expression, and 74 with decreased expression. Among the down-regulated were genes for DNA repair and oxidative stress tolerance response. These results suggest that XRE (SMU.405c) in S. mutans plays an important role in brpA expression and oxidative stress tolerance response.IMPORTANCEStreptococcus mutans, a keystone pathogen in human dental caries, primarily lives in the highly diverse microbiota on tooth surfaces, where the conditions are often harsh and fluctuate frequently. Locus SMU.405c was annotated to encode a xenobiotic response element (XRE)-like transcriptional regulator, but no information is available concerning the role of this protein in S. mutans pathophysiology. This study used a functional genomics approach along with molecular and transcriptomic analysis to characterize a deletional xre mutant, and the results showed that xre deficiency in S. mutans resulted in weakened oxidative stress tolerance response and alterations in transcription of >102 genes, including those known to play an important role in cell envelope biogenesis and stress tolerance response. Reporter fusion assay, electrophoretic mobility shift assay (EMSA), and in vitro transcription further demonstrated that the XRE-like regulator encoded by SMU.405c is a repressor of brpA expression and plays an important role in oxidative stress tolerance response. |
| Competing Interests: | The authors declare no conflict of interest. |
| References: | Mol Microbiol. 2020 Oct;114(4):681-693. (PMID: 32706915) Appl Environ Microbiol. 2012 Apr;78(8):2914-22. (PMID: 22327589) Proc Natl Acad Sci U S A. 2002 Oct 29;99(22):14434-9. (PMID: 12397186) J Bacteriol. 2015 Jul;197(13):2160-2170. (PMID: 25897032) Microbiology (Reading). 2013 Mar;159(Pt 3):493-506. (PMID: 23288544) Front Microbiol. 2021 Jun 24;12:671533. (PMID: 34248879) Appl Environ Microbiol. 2010 Sep;76(17):5815-26. (PMID: 20639370) J Bacteriol. 2021 Mar 22;203(11):. (PMID: 33753467) Front Cell Infect Microbiol. 2024 Nov 27;14:1499476. (PMID: 39664495) Front Cell Infect Microbiol. 2019 Jan 10;8:452. (PMID: 30687648) Nucleic Acids Res. 2020 Mar 18;48(5):2388-2400. (PMID: 31925438) PLoS Genet. 2023 Nov 16;19(11):e1011048. (PMID: 37972151) Mol Microbiol. 2025 May;123(5):433-438. (PMID: 40070161) J Biol Chem. 2006 Aug 4;281(31):21720-21727. (PMID: 16751195) Appl Environ Microbiol. 2002 Mar;68(3):1196-203. (PMID: 11872468) Microbiol Spectr. 2022 Dec 21;10(6):e0351122. (PMID: 36445133) PLoS One. 2012;7(9):e44766. (PMID: 23028612) Nat Biotechnol. 2019 Aug;37(8):907-915. (PMID: 31375807) J Bacteriol. 2023 Feb 22;205(2):e0046522. (PMID: 36695594) mSystems. 2022 Apr 26;7(2):e0127221. (PMID: 35289653) Infect Immun. 2005 Jan;73(1):219-25. (PMID: 15618157) Appl Environ Microbiol. 2017 Aug 17;83(17):. (PMID: 28687645) Trends Microbiol. 2018 Mar;26(3):229-242. (PMID: 29097091) J Dent Res. 1998 Mar;77(3):445-52. (PMID: 9496917) FEMS Microbiol Lett. 2011 Jul;320(2):110-7. (PMID: 21521360) Microbiology (Reading). 2008 Nov;154(Pt 11):3247-3255. (PMID: 18957579) Mutat Res. 1990 Sep-Nov;236(2-3):203-11. (PMID: 2204825) Microbiol Spectr. 2019 Jan;7(1):. (PMID: 30657107) J Bacteriol. 2006 Apr;188(8):2983-92. (PMID: 16585759) Annu Rev Biochem. 2018 Jun 20;87:677-696. (PMID: 29648875) Front Cell Infect Microbiol. 2017 Dec 20;7:524. (PMID: 29326887) Arch Microbiol. 2022 Apr 6;204(5):244. (PMID: 35386008) Mol Oral Microbiol. 2018 Oct;33(5):353-363. (PMID: 29888871) Mol Microbiol. 2005 Jul;57(2):392-404. (PMID: 15978073) Microb Cell Fact. 2020 Oct 2;19(1):189. (PMID: 33008408) J Bacteriol. 2004 May;186(9):2682-91. (PMID: 15090509) mSystems. 2021 Jan 12;6(1):. (PMID: 33436508) Front Microbiol. 2014 Jul 01;5:328. (PMID: 25071741) Mol Oral Microbiol. 2017 Dec;32(6):517-525. (PMID: 28744965) J Bacteriol. 2005 Jul;187(13):4392-400. (PMID: 15968048) Microbiol Spectr. 2025 Jun 3;13(6):e0330124. (PMID: 40272195) |
| Grant Information: | R01 DE019452 United States DE NIDCR NIH HHS; R21 DE031856 United States DE NIDCR NIH HHS; DE019452 United States DE NIDCR NIH HHS; DE019452 UniCredit and Universities Foundation |
| Contributed Indexing: | Keywords: S. mutans; XRE; biofilm formation; brpA expression; oxidative stress tolerance response |
| Substance Nomenclature: | 0 (Bacterial Proteins) 0 (BrpA protein, Streptococcus mutans) BBX060AN9V (Hydrogen Peroxide) |
| Entry Date(s): | Date Created: 20260721 Date Completed: 20260902 Latest Revision: 20260903 |
| Update Code: | 20260903 |
| PubMed Central ID: | PMC13532258 |
| DOI: | 10.1128/spectrum.00116-26 |
| PMID: | 42478824 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 2165-0497 |
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| DOI: | 10.1128/spectrum.00116-26 |