Triton X-100 counteracts antibiotic resistance of Enterococcus faecalis: An in vitro study

Xinling He; Shujie Xv; Runze Liu; Mengting Duan; Wei Fan; Bing Fan

doi:10.1016/j.jdent.2024.105046

Triton X-100 counteracts antibiotic resistance of Enterococcus faecalis: An in vitro study

J Dent. 2024 May 8:146:105046. doi: 10.1016/j.jdent.2024.105046. Online ahead of print.

Authors

Xinling He¹, Shujie Xv¹, Runze Liu¹, Mengting Duan¹, Wei Fan², Bing Fan³

Affiliations

¹ 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.
² 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. Electronic address: weifan@whu.edu.cn.
³ 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. Electronic address: bingfan@whu.edu.cn.

PMID: 38729285
DOI: 10.1016/j.jdent.2024.105046

Abstract

Objectives: 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).

Methods: 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.

Results: 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.

Conclusions: 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.

Clinical significance: These findings provide a theoretical basis for developing new root canal disinfectants that can reduce antibiotic resistance.

Keywords: Antibiotics; Enterococcus faecalis; Metabolic regulation; Resistance; Triton X-100.