Metformin reduced the alkaline resistance of Enterococcus faecalis against calcium hydroxide via Man-PTS EII: in vitro and in vivo studies

IF 3.1 2区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Clinical Oral Investigations Pub Date : 2024-09-10 DOI:10.1007/s00784-024-05909-7

Runze Liu, Pei Liu, Yi Luo, Wei Fan, Bing Fan

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Abstract

Objectives

The mannose phosphotransferase system (Man-PTS) plays crucial roles in the adaptive metabolic activity of Enterococcus faecalis (E. faecalis) in adverse environments. The aim of this study was to evaluate the role of Man-PTS in the alkaline resistance of E. faecalis against calcium hydroxide (CH) and the effect of metformin (Met) on the alkaline resistance of E. faecalis to CH.

Materials and methods

The regulatory role of Man-PTS EII in the alkaline resistance of E. faecalis was firstly investigated using a wild-type highly alkaline-resistant E. faecalis XS 003, standard ATCC 29212 and Man-PTS EIID gene deficient (△mptD) and overexpressing (+mptD) strains of E. faecalis. RNA sequencing of Met-treated E. faecalis was performed to further validate the effect of Met on Man-PTS. The effect of Met on CH resistance of E. faecalis was verified by evaluating the survival, membrane potential and permeability, intracellular pH and ATP, and the expression of Man-PTS EII and membrane transporter-related genes of E. faecalis. The effect of Met on the ability of CH to remove E. faecalis biofilm on the dentin surface was also tested. The in vivo therapeutic effect of Met plus CH (CHM) was further investigated in a rat apical periodontitis model induced by E. faecalis XS 003.

Results

Man-PTS EII significantly promoted the survival ability of E. faecalis in CH and enhanced its resistance to CH. The inhibition of Man-PTS EII by Met resulted in reduced alkaline resistance of E. faecalis in the presence of CH, while also enhancing the antimicrobial properties of CH against E. faecalis biofilm on dentin. Additionally, Met plus CH showed the synergistically promoted intra-canal E. faecalis infection control and healing of periapical lesion in rats.

Conclusions

Met could significantly reduce the alkaline resistance of E. faecalis against CH through the modulation of Man-PTS EII, and improved the antibacterial effect of CH against E. faecalis infection both in vitro and in vivo.

Clinical relevance

Met could significantly enhance the ability of CH to control E. faecalis infection through reducing the alkaline resistance of E. faecalis.

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二甲双胍通过 Man-PTS EII 降低粪肠球菌对氢氧化钙的耐碱性：体外和体内研究

目的甘露糖磷酸转移酶系统（Man-PTS）在粪肠球菌（E. faecalis）在不利环境中的适应性代谢活动中起着至关重要的作用。本研究旨在评估 Man-PTS 在粪肠球菌对氢氧化钙（CH）的耐碱性中的作用，以及二甲双胍（Met）对粪肠球菌对 CH 的耐碱性的影响。材料和方法首先使用野生型高抗碱性粪肠球菌 XS 003、标准 ATCC 29212 和 Man-PTS EIID 基因缺失（△mptD）和过表达（+mptD）菌株研究 Man-PTS EII 在粪肠球菌抗碱性中的调控作用。为了进一步验证 Met 对 Man-PTS 的影响，对 Met 处理过的粪肠球菌进行了 RNA 测序。通过评估粪肠球菌的存活率、膜电位和通透性、细胞内 pH 和 ATP 以及 Man-PTS EII 和膜转运体相关基因的表达，验证了 Met 对粪肠球菌耐 CH 能力的影响。此外，还测试了 Met 对 CH 清除牙本质表面的粪大肠杆菌生物膜能力的影响。结果 Man-PTS EII 显著提高了粪大肠杆菌在 CH 中的存活能力，并增强了其对 CH 的抵抗力。Met 对 Man-PTS EII 的抑制作用降低了粪大肠杆菌在 CH 中的耐碱性，同时也增强了 CH 对牙本质上的粪大肠杆菌生物膜的抗菌性。结论Met 可通过调节 Man-PTS EII 显著降低粪肠球菌对 CH 的耐碱性，并提高 CH 在体外和体内对粪肠球菌感染的抗菌效果。

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来源期刊

Clinical Oral Investigations 医学-牙科与口腔外科

CiteScore

6.30

自引率

5.90%

发文量

484

审稿时长

3 months

期刊介绍： The journal Clinical Oral Investigations is a multidisciplinary, international forum for publication of research from all fields of oral medicine. The journal publishes original scientific articles and invited reviews which provide up-to-date results of basic and clinical studies in oral and maxillofacial science and medicine. The aim is to clarify the relevance of new results to modern practice, for an international readership. Coverage includes maxillofacial and oral surgery, prosthetics and restorative dentistry, operative dentistry, endodontics, periodontology, orthodontics, dental materials science, clinical trials, epidemiology, pedodontics, oral implant, preventive dentistiry, oral pathology, oral basic sciences and more.