Effects of S. mutans gene-modification and antibacterial monomer dimethylaminohexadecyl methacrylate on biofilm growth and acid production

Hong Chen; Yunhao Tang; Michael D Weir; Jianghong Gao; Satoshi Imazato; Thomas W Oates; Lei Lei; Suping Wang; Tao Hu; Hockin H K Xu

doi:10.1016/j.dental.2019.12.001

Effects of S. mutans gene-modification and antibacterial monomer dimethylaminohexadecyl methacrylate on biofilm growth and acid production

Dent Mater. 2020 Feb;36(2):296-309. doi: 10.1016/j.dental.2019.12.001. Epub 2019 Dec 12.

Authors

Hong Chen¹, Yunhao Tang², Michael D Weir³, Jianghong Gao⁴, Satoshi Imazato⁵, Thomas W Oates³, Lei Lei⁶, Suping Wang⁷, Tao Hu⁸, Hockin H K Xu⁹

Affiliations

¹ State Key Laboratory of Oral Diseases, Department of Preventive Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China; Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, MD 21201, USA.
² Department of Gastrointestinal Surgery, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
³ Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, MD 21201, USA.
⁴ Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, MD 21201, USA; Clinical Research Center of Shaanxi Province for Dental and Maxillofacial Diseases, Department of Preventive Dentistry, College of Stomatology, Xi'an Jiaotong University, Xi'an, 710004, China.
⁵ Department of Biomaterials Science, Osaka University Graduate School of Dentistry, Osaka, Japan.
⁶ State Key Laboratory of Oral Diseases, Department of Preventive Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China.
⁷ Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, MD 21201, USA; Department of Operative Dentistry and Endodontics & Periodontics and Stomatology Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China. Electronic address: wangsupingdent@163.com.
⁸ State Key Laboratory of Oral Diseases, Department of Preventive Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China. Electronic address: hutao@scu.edu.cn.
⁹ Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, MD 21201, USA; Center for Stem Cell Biology & Regenerative Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA. Electronic address: hxu@umaryland.edu.

PMID: 31839202
DOI: 10.1016/j.dental.2019.12.001

Abstract

Objectives: Antibacterial quaternary ammonium monomers (QAMs) are used in resins. The rnc gene in Streptococcus mutans (S. mutans) plays a key role in resisting antibiotics. The objectives of this study were to investigate for the first time: (1) the effects of rnc deletion on S. mutans biofilms and acid production; (2) the combined effects of rnc deletion with dimethylaminohexadecyl methacrylate (DMAHDM) on biofilm-inhibition efficacy.

Methods: Parent S. mutans strain UA159 (ATCC 700610) and the rnc-deleted S. mutans were used. Bacterial growth, minimum inhibitory concentration (MIC), and minimal bactericidal concentration (MBC) were measured to analyze the bacterial susceptibility of the parent and rnc-deleted S. mutans against DMAHDM, with the gold-standard chlorhexidine (CHX) as control. Biofilm biomass, polysaccharide and lactic acid production were measured.

Results: The drug-susceptibility of the rnc-deleted S. mutans to DMAHDM or CHX was 2-fold higher than parent S. mutans. The drug-susceptibility did not increase after 10 passages (p < 0.05). Deleting the rnc gene increased the biofilm susceptibility to DMAHDM or CHX by 2-fold. The rnc-deletion in S. mutans reduced biofilm biomass, polysaccharide and lactic acid production, even at no drugs. DMAHDM was nearly 40 % more potent than the gold-standard CHX. The combination of rnc deletion+DMAHDM treatment achieved the greatest reduction in biofilm biomass, polysaccharide synthesis, and lactic acid production.

Significance: Gene modification by deleting the rnc in S. mutans reduced the biofilm growth and acid production, and the rnc deletion+DMAHDM method showed the greatest biofilm-inhibition efficacy, for the first time. The dual strategy of antibacterial monomer+bacterial gene modification shows great potential to control biofilms and inhibit caries.

Keywords: Dental caries.; Dimethylaminohexadecyl; Lactic acid; Methacrylate; Quaternary ammonium; Streptococcus mutans; rnc gene modification.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents
Biofilms*
Methacrylates
Microbial Sensitivity Tests
Streptococcus mutans*

Substances

Anti-Bacterial Agents
Methacrylates