title: Effects of intracanal irrigant MTAD Combined with nisin at sub-minimum inhibitory concentration levels on Enterococcus faecalis growth and the expression of pathogenic genes.
abstract: Exposure to antibiotics is considered to be the major driver in the selection of antibiotic-resistant bacteria and may induce diverse biological responses in bacteria. MTAD is a common intracanal irrigant, but its bactericidal activity remains to be improved. Previous studies have indicated that the antimicrobial peptide nisin can significantly improve the bactericidal activity of MTAD against Enterococcus faecalis. However, the effects of MTAD and its modification at sub-minimum inhibitory concentration (sub-MIC) levels on Enterococcus faecalis growth and the expression of pathogenic genes still need to be explored. In this study, the results of post-antibiotic effects (PAE) and post-antibiotic sub-MIC effects (PASME) showed that MTADN (nisin in combination with MTAD) had the best post-antibiotic effect. E. faecalis after challenge with MTAD was less sensitive to alkaline solutions compared with MTAN (nisin in place of doxycycline in MTAD) and MTADN. E. faecalis induced with sub-MIC of MTAD generated resistance to the higher concentration, but induction of E. faecalis with MTAN did not cause resistance to higher concentrations. Furthermore, real-time polymerase chain reaction (RT-PCR) showed that the stress caused by sub-MIC exposure to MTAD, MTAN, or MTADN resulted in up- or down-regulation of nine stress genes and four virulence-associated genes in E. faecalis and resulted in different stress states. These findings suggested that nisin improved the post-antibacterial effect of MTAD at sub-MIC levels and has considerable potential for use as a modification of MTAD.
authors.affiliation: Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China; Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Zhongchun
authors.initials: Z
authors.lastname: Tong
authors.affiliation: Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Lijia
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China; Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Junqi
authors.initials: J
authors.lastname: Ling
authors.affiliation: Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Xueli
authors.initials: X
authors.lastname: Mao
authors.affiliation: Department of Periodontology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Ning
authors.affiliation: Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China; Department of Cariology Endodontology Pedodontology, Academic Centre for Dentistry Amsterdam (ACTA), Universiteit van Amsterdam and Vrije Universiteit, Amsterdam, The Netherlands.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Deng
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D019343:Citric Acid / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004318:Doxycycline / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D004357:Drug Synergism; D013293:Enterococcus faecalis / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects / Q000235:genetics; D009561:Nisin / Q000494:pharmacology*; D011136:Polysorbates / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012388:Root Canal Irrigants / Q000494:pharmacology*; D014774:Virulence / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D011136:Polysorbates; D012388:Root Canal Irrigants; D009561:Nisin; D019343:Citric Acid; C102526:nisin A; D004318:Doxycycline