The State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China.
The State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China.
J Dent. 2024 Jul;146:105046. doi: 10.1016/j.jdent.2024.105046. Epub 2024 May 8.
The high prevalence of antibiotic-resistant bacteria poses a threat to the global public health. The appropriate use of adjuvants to restore the antimicrobial activity of antibiotics against resistant bacteria could be an effective strategy for combating antibiotic resistance. In this study, we investigated the counteraction of Triton X-100 (TX-100) and the mechanisms underlying the antibiotic resistance of Enterococcus faecalis (E. faecalis).
Standard, wild-type (WT), and induced antibiotic-resistant E. faecalis strains were used in this study. In vitro antibacterial experiments were conducted to evaluate the antimicrobial activities of gentamicin sulfate and ciprofloxacin hydrochloride in the presence and absence of 0.02 % TX-100 against both planktonic and biofilm bacteria. Transcriptomic and untargeted metabolomic analyses were performed to explore the molecular mechanisms of TX-100 as an antibiotic adjuvant. Additionally, membrane permeability, membrane potential, glycolysis-related enzyme activity, intracellular adenosine triphosphate (ATP), and expression levels of virulence genes were assessed. The biocompatibility of different drug combinations was also evaluated.
A substantially low TX-100 concentration improved the antimicrobial effects of gentamicin sulfate or ciprofloxacin hydrochloride against antibiotic-resistant E. faecalis. Mechanistic studies demonstrated that TX-100 increased cell membrane permeability and dissipated membrane potential. Moreover, antibiotic resistance and pathogenicity of E. faecalis were attenuated by TX-100 via downregulation of the ABC transporter, phosphotransferase system (PTS), and ATP supply.
TX-100 enhanced the antimicrobial activity of gentamicin sulfate and ciprofloxacin hydrochloride at a low concentration by improving antibiotic susceptibility and attenuating antibiotic resistance and pathogenicity of E. faecalis.
These findings provide a theoretical basis for developing new root canal disinfectants that can reduce antibiotic resistance.
抗生素耐药菌的高流行率对全球公共健康构成威胁。适当使用佐剂来恢复抗生素对耐药菌的抗菌活性可能是对抗抗生素耐药性的有效策略。在本研究中，我们研究了 Triton X-100（TX-100）的反作用以及粪肠球菌（E. faecalis）抗生素耐药性的潜在机制。
本研究使用标准、野生型（WT）和诱导的抗生素耐药粪肠球菌菌株。进行体外抗菌实验以评估硫酸庆大霉素和盐酸环丙沙星在存在和不存在 0.02%TX-100 时对浮游和生物膜细菌的抗菌活性。进行转录组和非靶向代谢组学分析以探索 TX-100 作为抗生素佐剂的分子机制。此外，评估了膜通透性、膜电位、糖酵解相关酶活性、细胞内三磷酸腺苷（ATP）和毒力基因的表达水平。还评估了不同药物组合的生物相容性。
低浓度的 TX-100 大大提高了硫酸庆大霉素或盐酸环丙沙星对抗生素耐药粪肠球菌的抗菌效果。机制研究表明，TX-100 增加了细胞膜通透性并耗散了膜电位。此外，通过下调 ABC 转运蛋白、磷酸转移酶系统（PTS）和 ATP 供应，TX-100 降低了粪肠球菌的抗生素耐药性和致病性，从而减弱了其抗生素耐药性和致病性。
TX-100 通过提高抗生素敏感性并减弱粪肠球菌的抗生素耐药性和致病性，在低浓度下增强了硫酸庆大霉素和盐酸环丙沙星的抗菌活性。
这些发现为开发可降低抗生素耐药性的新根管消毒剂提供了理论依据。
