Maione Angela, La Pietra Alessandra, de Alteriis Elisabetta, Mileo Aldo, De Falco Maria, Guida Marco, Galdiero Emilia
Department of Biology, University of Naples 'Federico II', Via Cinthia, 80126 Naples, Italy.
National Institute of Biostructures and Biosystems (INBB), 00136 Rome, Italy.
Microorganisms. 2022 Sep 2;10(9):1773. doi: 10.3390/microorganisms10091773.
The increased incidence of mixed infections requires that the scientific community develop novel antimicrobial molecules. Essential oils and their bioactive pure compounds have been found to exhibit a wide range of remarkable biological activities and are attracting more and more attention. Therefore, the aim of this study was to evaluate myrtenol (MYR), one of the constituents commonly found in some essential oils, for its potential to inhibit biofilms alone and in combination with antimicrobial drugs against / single and mixed biofilms. The antimicrobial activity of MYR was evaluated by determining bactericidal/fungicidal concentrations (MIC), and biofilm formation at sub-MICs was analyzed in a 96-well microtiter plate by crystal violet, XTT reduction assay, and CFU counts. The synergistic interaction between MYR and antimicrobial drugs was evaluated by the checkerboard method. The study found that MYR exhibited antimicrobial activity at high concentrations while showing efficient antibiofilm activity against single and dual biofilms. To understand the underlying mechanism by which MYR promotes single/mixed-species biofilm inhibition, we observed a significant downregulation in the expression of , , , and genes, which are associated with bacterial motility, adhesion, and biofilm formation as well as increased ROS production, which can play an important role in the inhibition of biofilm formation. In addition, the checkerboard microdilution assay showed that MYR was strongly synergistic with both caspofungin (CAS) and meropenem (MEM) in inhibiting the growth of /-mixed biofilms. Furthermore, the tested concentrations showed an absence of toxicity for both mammalian cells in the in vitro and in vivo models. Thus, MYR could be considered as a potential agent for the management of polymicrobial biofilms.
混合感染发病率的增加要求科学界开发新型抗菌分子。人们发现精油及其具有生物活性的纯化合物具有广泛的显著生物活性，并且越来越受到关注。因此，本研究的目的是评估桃金娘烯醇（MYR），它是一些精油中常见的成分之一，研究其单独以及与抗菌药物联合抑制生物膜对抗单一和混合生物膜的潜力。通过测定杀菌/杀真菌浓度（MIC）来评估MYR的抗菌活性，并在96孔微量滴定板中通过结晶紫、XTT还原测定法和菌落形成单位计数分析亚MIC浓度下的生物膜形成。通过棋盘法评估MYR与抗菌药物之间的协同相互作用。研究发现，MYR在高浓度时表现出抗菌活性，同时对单一和双重生物膜显示出有效的抗生物膜活性。为了了解MYR促进单一/混合物种生物膜抑制的潜在机制，我们观察到与细菌运动性、粘附和生物膜形成相关的 、 、 和 基因的表达显著下调，以及活性氧产生增加，这在抑制生物膜形成中可发挥重要作用。此外，棋盘微量稀释试验表明，MYR在抑制 /混合生物膜生长方面与卡泊芬净（CAS）和美罗培南（MEM）均具有强烈的协同作用。此外，所测试的浓度在体外和体内模型中对两种哺乳动物细胞均未显示出毒性。因此，MYR可被视为一种管理多微生物生物膜的潜在药物。
