{"title":"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","authors":"Runze Liu, Pei Liu, Yi Luo, Wei Fan, Bing Fan","doi":"10.1007/s00784-024-05909-7","DOIUrl":null,"url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Objectives</h3><p>The mannose phosphotransferase system (Man-PTS) plays crucial roles in the adaptive metabolic activity of <i>Enterococcus faecalis</i> (<i>E. faecalis</i>) in adverse environments. The aim of this study was to evaluate the role of Man-PTS in the alkaline resistance of <i>E. faecalis</i> against calcium hydroxide (CH) and the effect of metformin (Met) on the alkaline resistance of <i>E. faecalis</i> to CH.</p><h3 data-test=\"abstract-sub-heading\">Materials and methods</h3><p>The regulatory role of Man-PTS EII in the alkaline resistance of <i>E. faecalis</i> was firstly investigated using a wild-type highly alkaline-resistant <i>E. faecalis</i> XS 003, standard ATCC 29212 and Man-PTS EIID gene deficient (△<i>mptD</i>) and overexpressing (+<i>mptD</i>) strains of <i>E. faecalis</i>. RNA sequencing of Met-treated <i>E. faecalis</i> was performed to further validate the effect of Met on Man-PTS. The effect of Met on CH resistance of <i>E. faecalis</i> 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 <i>E. faecalis</i>. The effect of Met on the ability of CH to remove <i>E. faecalis</i> 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 <i>E. faecalis</i> XS 003.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Man-PTS EII significantly promoted the survival ability of <i>E. faecalis</i> in CH and enhanced its resistance to CH. The inhibition of Man-PTS EII by Met resulted in reduced alkaline resistance of <i>E. faecalis</i> in the presence of CH, while also enhancing the antimicrobial properties of CH against <i>E. faecalis</i> biofilm on dentin. Additionally, Met plus CH showed the synergistically promoted intra-canal <i>E. faecalis</i> infection control and healing of periapical lesion in rats.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>Met could significantly reduce the alkaline resistance of <i>E. faecalis</i> against CH through the modulation of Man-PTS EII, and improved the antibacterial effect of CH against <i>E. faecalis</i> infection both in vitro and in vivo.</p><h3 data-test=\"abstract-sub-heading\">Clinical relevance</h3><p>Met could significantly enhance the ability of CH to control <i>E. faecalis</i> infection through reducing the alkaline resistance of <i>E. faecalis</i>.</p>","PeriodicalId":10461,"journal":{"name":"Clinical Oral Investigations","volume":null,"pages":null},"PeriodicalIF":3.1000,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Metformin reduced the alkaline resistance of Enterococcus faecalis against calcium hydroxide via Man-PTS EII: in vitro and in vivo studies\",\"authors\":\"Runze Liu, Pei Liu, Yi Luo, Wei Fan, Bing Fan\",\"doi\":\"10.1007/s00784-024-05909-7\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<h3 data-test=\\\"abstract-sub-heading\\\">Objectives</h3><p>The mannose phosphotransferase system (Man-PTS) plays crucial roles in the adaptive metabolic activity of <i>Enterococcus faecalis</i> (<i>E. faecalis</i>) in adverse environments. The aim of this study was to evaluate the role of Man-PTS in the alkaline resistance of <i>E. faecalis</i> against calcium hydroxide (CH) and the effect of metformin (Met) on the alkaline resistance of <i>E. faecalis</i> to CH.</p><h3 data-test=\\\"abstract-sub-heading\\\">Materials and methods</h3><p>The regulatory role of Man-PTS EII in the alkaline resistance of <i>E. faecalis</i> was firstly investigated using a wild-type highly alkaline-resistant <i>E. faecalis</i> XS 003, standard ATCC 29212 and Man-PTS EIID gene deficient (△<i>mptD</i>) and overexpressing (+<i>mptD</i>) strains of <i>E. faecalis</i>. RNA sequencing of Met-treated <i>E. faecalis</i> was performed to further validate the effect of Met on Man-PTS. The effect of Met on CH resistance of <i>E. faecalis</i> 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 <i>E. faecalis</i>. The effect of Met on the ability of CH to remove <i>E. faecalis</i> 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 <i>E. faecalis</i> XS 003.</p><h3 data-test=\\\"abstract-sub-heading\\\">Results</h3><p>Man-PTS EII significantly promoted the survival ability of <i>E. faecalis</i> in CH and enhanced its resistance to CH. The inhibition of Man-PTS EII by Met resulted in reduced alkaline resistance of <i>E. faecalis</i> in the presence of CH, while also enhancing the antimicrobial properties of CH against <i>E. faecalis</i> biofilm on dentin. Additionally, Met plus CH showed the synergistically promoted intra-canal <i>E. faecalis</i> infection control and healing of periapical lesion in rats.</p><h3 data-test=\\\"abstract-sub-heading\\\">Conclusions</h3><p>Met could significantly reduce the alkaline resistance of <i>E. faecalis</i> against CH through the modulation of Man-PTS EII, and improved the antibacterial effect of CH against <i>E. faecalis</i> infection both in vitro and in vivo.</p><h3 data-test=\\\"abstract-sub-heading\\\">Clinical relevance</h3><p>Met could significantly enhance the ability of CH to control <i>E. faecalis</i> infection through reducing the alkaline resistance of <i>E. faecalis</i>.</p>\",\"PeriodicalId\":10461,\"journal\":{\"name\":\"Clinical Oral Investigations\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.1000,\"publicationDate\":\"2024-09-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical Oral Investigations\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s00784-024-05909-7\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"DENTISTRY, ORAL SURGERY & MEDICINE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Oral Investigations","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00784-024-05909-7","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"DENTISTRY, ORAL SURGERY & MEDICINE","Score":null,"Total":0}
Metformin reduced the alkaline resistance of Enterococcus faecalis against calcium hydroxide via Man-PTS EII: in vitro and in vivo studies
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.
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.