A New Small Molecule Inhibits Streptococcus Mutans Biofilms in Vitro and in Vivo

Overview

Journal J Appl Microbiol

Publisher Oxford University Press

Date 2015 Aug 22

PMID 26294263

Citations 12

Authors

W Pan

M Fan

H Wu

C Melander

C Liu

Affiliations

Soon will be listed here.

Abstract

Aims: The aim of this study was to identify new small molecules that can inhibit Streptococcus mutans biofilms by in vitro and in vivo model.

Methods And Results: We evaluated the effect of a small molecule 2-amino-imidazole/triazole conjugate (2-AI/T) on the formation of Strep. mutans biofilms by culturing in 96-well plates. Toxicity was assessed through cell culture and intragastrically administering to mice. The anti-biofilm and anti-caries effects were investigated in vivo. The inhibitive mechanism was detected by isobaric tag for relative and absolute quantification (itraq) and RT-QPCR. In vitro and in vivo study revealed that 2-AI/T significantly inhibited biofilm formation of Strep. mutans and is more so than inhibiting planktonic cells without toxicity. The ribosome and histidine metabolism pathways of Strep. mutans were significantly regulated by this compound.

Conclusions: These results suggest that the 2-AI/T conjugate is a potent inhibitor that can be potentially developed into a new drug to treat and prevent dental caries.

Significance And Impact Of The Study: This is the first study to use small molecule from marine natural products, to protect from dental caries in vivo. It has potential broad range application in clinical caries prevention, or as a bioactive ingredient for food applications.

Citing Articles

Association of polymicrobial interactions with dental caries development and prevention.

Zhu Y, Wang Y, Zhang S, Li J, Li X, Ying Y Front Microbiol. 2023; 14:1162380.

PMID: 37275173 PMC: 10232826. DOI: 10.3389/fmicb.2023.1162380.

Discovery of Novel Iminosugar Compounds Produced by MJM60645 and Their Anti-Biofilm Activity against Streptococcus mutans.

Gu M, Cheng J, Lee Y, Cho J, Suh J Microbiol Spectr. 2022; 10(4):e0112222.

PMID: 35863019 PMC: 9431463. DOI: 10.1128/spectrum.01122-22.

Anti-biofilm studies of synthetic imidazolium salts on dental biofilm in vitro.

Pan T, Liu F, Lin H, Zhou Y J Oral Microbiol. 2022; 14(1):2075309.

PMID: 35600163 PMC: 9116249. DOI: 10.1080/20002297.2022.2075309.

Development of small molecules that work cooperatively with ciprofloxacin to clear salmonella biofilms in a chronic gallbladder carriage model.

Woolard K, Sandala J, Melander R, Gunn J, Melander C Eur J Med Chem. 2022; 232:114203.

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Oral mucosa and Streptococcus mutans count in the saliva. Does graphene oxide nanoparticle mouthwash have a good effect?.

Eshaghi Gorji F, Seyedmajidi M, Asgharpours F, Tashakorian H, Moghadamnia A, Kazemi S Caspian J Intern Med. 2021; 12(3):342-349.

PMID: 34221286 PMC: 8223048. DOI: 10.22088/cjim.12.3.342.

References

Ikeno K, Ikeno T, Miyazawa C . Effects of propolis on dental caries in rats. Caries Res. 1991; 25(5):347-51. DOI: 10.1159/000261390. View

Mackay B, Denepitiya L, Iacono V, Krost S, Pollock J . Growth-inhibitory and bactericidal effects of human parotid salivary histidine-rich polypeptides on Streptococcus mutans. Infect Immun. 1984; 44(3):695-701. PMC: 263672. DOI: 10.1128/iai.44.3.695-701.1984. View

Wilkins J, Homer K, Beighton D . Analysis of Streptococcus mutans proteins modulated by culture under acidic conditions. Appl Environ Microbiol. 2002; 68(5):2382-90. PMC: 127557. DOI: 10.1128/AEM.68.5.2382-2390.2002. View

Doron S, Friedman M, Falach M, Sadovnic E, Zvia H . Antibacterial effect of parabens against planktonic and biofilm Streptococcus sobrinus. Int J Antimicrob Agents. 2001; 18(6):575-8. DOI: 10.1016/s0924-8579(01)00436-8. View

Dierickx P . Cytotoxicity of the MEIC reference chemicals in rat hepatoma-derived Fa32 cells. Toxicology. 2000; 150(1-3):159-69. DOI: 10.1016/s0300-483x(00)00255-9. View

Loo C, Corliss D, Ganeshkumar N . Streptococcus gordonii biofilm formation: identification of genes that code for biofilm phenotypes. J Bacteriol. 2000; 182(5):1374-82. PMC: 94426. DOI: 10.1128/JB.182.5.1374-1382.2000. View

Skropeta D, Wei L . Recent advances in deep-sea natural products. Nat Prod Rep. 2014; 31(8):999-1025. DOI: 10.1039/c3np70118b. View

Otake S, Makimura M, Kuroki T, Nishihara Y, Hirasawa M . Anticaries effects of polyphenolic compounds from Japanese green tea. Caries Res. 1991; 25(6):438-43. DOI: 10.1159/000261407. View

Barile F, Cardona M . Acute cytotoxicity testing with cultured human lung and dermal cells. In Vitro Cell Dev Biol Anim. 1998; 34(8):631-5. DOI: 10.1007/s11626-996-0011-0. View

10.

Keyes P . Dental caries in the molar teeth of rats. I. Distribution of lesions induced by high-carbohydrate low-fat diets. J Dent Res. 1958; 37(6):1077-87. DOI: 10.1177/00220345580370060801. View

11.

Wang B, Feng W, Wang T, Jia G, Wang M, Shi J . Acute toxicity of nano- and micro-scale zinc powder in healthy adult mice. Toxicol Lett. 2005; 161(2):115-23. DOI: 10.1016/j.toxlet.2005.08.007. View

12.

Tam A, Shemesh M, Wormser U, Sintov A, Steinberg D . Effect of different iodine formulations on the expression and activity of Streptococcus mutans glucosyltransferase and fructosyltransferase in biofilm and planktonic environments. J Antimicrob Chemother. 2006; 57(5):865-71. DOI: 10.1093/jac/dkl085. View

13.

Mattos-Graner R, Porter K, Smith D, Hosogi Y, Duncan M . Functional analysis of glucan binding protein B from Streptococcus mutans. J Bacteriol. 2006; 188(11):3813-25. PMC: 1482924. DOI: 10.1128/JB.01845-05. View

14.

Musk Jr D, Hergenrother P . Chemical countermeasures for the control of bacterial biofilms: effective compounds and promising targets. Curr Med Chem. 2006; 13(18):2163-77. DOI: 10.2174/092986706777935212. View

15.

Forte B, Malgesini B, Piutti C, Quartieri F, Scolaro A, Papeo G . A submarine journey: the pyrrole-imidazole alkaloids. Mar Drugs. 2010; 7(4):705-53. PMC: 2810223. DOI: 10.3390/md7040705. View

16.

Liu C, Fan M, Bian Z, Chen Z, Li Y . Effects of targeted fusion anti-caries DNA vaccine pGJA-P/VAX in rats with caries. Vaccine. 2008; 26(51):6685-9. DOI: 10.1016/j.vaccine.2008.08.041. View

17.

Ballard T, Richards J, Aquino A, Reed C, Melander C . Antibiofilm activity of a diverse oroidin library generated through reductive acylation. J Org Chem. 2009; 74(4):1755-8. DOI: 10.1021/jo802260t. View

18.

Richards J, Ballard T, Melander C . Inhibition and dispersion of Pseudomonas aeruginosa biofilms with reverse amide 2-aminoimidazole oroidin analogues. Org Biomol Chem. 2008; 6(8):1356-63. DOI: 10.1039/b719082d. View

19.

Huigens 3rd R, Richards J, Parise G, Ballard T, Zeng W, Deora R . Inhibition of Pseudomonas aeruginosa biofilm formation with Bromoageliferin analogues. J Am Chem Soc. 2007; 129(22):6966-7. DOI: 10.1021/ja069017t. View

20.

Simionato M, Tucker C, Kuboniwa M, Lamont G, Demuth D, Tribble G . Porphyromonas gingivalis genes involved in community development with Streptococcus gordonii. Infect Immun. 2006; 74(11):6419-28. PMC: 1695522. DOI: 10.1128/IAI.00639-06. View