目的:抗生素耐药菌的高流行对全球公众健康构成了威胁。适当使用佐剂来恢复抗生素对耐药细菌的抗微生物活性可能是对抗抗生素耐药性的有效策略。在这项研究中,我们调查了TritonX-100(TX-100)的反作用以及粪肠球菌对抗生素的耐药性的潜在机制(E.粪肠)。
方法:标准,野生型(WT),本研究使用诱导的耐抗生素粪肠球菌菌株。进行了体外抗菌实验,以评估在存在和不存在0.02%TX-100的情况下,硫酸庆大霉素和盐酸环丙沙星对浮游细菌和生物膜细菌的抗菌活性。进行转录组学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,膜渗透性,膜电位,糖酵解相关酶活性,细胞内三磷酸腺苷(ATP),并评估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。
结果:相当低的TX-100浓度提高了硫酸庆大霉素或盐酸环丙沙星对耐抗生素粪肠球菌的抗菌作用。机制研究表明,TX-100增加细胞膜通透性和耗散膜电位。此外,通过下调ABC转运蛋白,TX-100减弱粪肠球菌的抗生素抗性和致病性,磷酸转移酶系统(PTS),ATP供应。
结论:TX-100可通过改善抗生素敏感性、降低粪肠球菌的耐药性和致病性,增强低浓度硫酸庆大霉素和盐酸环丙沙星的抗菌活性。
结论:这些发现为开发能够降低抗生素耐药性的新型根管消毒剂提供了理论依据。
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.