First Evidence of a Combination of Terpinen-4-ol and α-Terpineol as a Promising Tool against ESKAPE Pathogens

Abstract

Antimicrobial resistance is a major public health issue raising growing concern in the face of dwindling response options. It is therefore urgent to find new anti-infective molecules enabling us to fight effectively against ever more numerous bacterial infections caused by ever more antibiotic-resistant bacteria. In this quest for new antibacterials, essential oils (or compounds extracted from essential oils) appear to be a promising therapeutic option. In the present work, we investigate the potential antibacterial synergy between a combination of terpinen-4-ol and α-terpineol (10:1) compared to standard tea tree oil. The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) were determined. Then, time kill assays, in vitro cytotoxicity and bactericidal activity on latent bacteria (persisters) were investigated. Finally, an in silico study of the pharmacokinetic parameters of α-terpineol was also performed. Altogether, our data demonstrate that the combination of terpinen-4-ol and α-terpineol might be a precious weapon to address ESKAPE pathogens.

Mixture design of α‐pinene, α‐terpineol, and 1,8‐cineole: A multiobjective response followed by chemometric approaches to optimize the antibacterial effect against various bacteria and antioxidant activity

“…Some studies have reported that α‐terpineol and terpinen‐4‐ol also showed potent antibacterial effects against gram‐positive bacteria, such as S. aureus , Streptococcus agalactiae (Johansen et al., 2022 ), Bacillus coagulans , and Micrococcus luteus (Kotan et al., 2007 ), suggesting that α‐terpineol and terpinen‐4‐ol are effective bacterial inhibitors with a broad bacterial spectrum. In the same context, previous publications have shown that 1,8‐cineole has relatively potent antimicrobial activity as a bactericide against many pathogens and spoilage organisms, such as S. aureus , P. aeruginosa , E. coli , and B. subtilis (Cai et al., 2021 ; Şimşek & Duman, 2017 ), but the antimicrobial mechanisms of 1,8‐cineole are still not completely clear.…”

“…On the other hand, α‐terpineol, by influencing the integrity and permeability of cell membranes, can lead to the collapse of the bacterial cell by dissolving the cell wall (Huang et al., 2021 ). Other studies on the mode of action of α‐terpineol have shown that it can act by blocking DNA, RNA, proteins, polysaccharide synthesis, ATP production, or the tricarboxylic acid cycle (Johansen et al., 2022 ; Khaleel et al., 2018 ).…”