Terpinen-4-ol as an Antibacterial and Antibiofilm Agent against Staphylococcus aureus

Abstract

Staphylococcus aureus is able to rapidly develop mechanisms of resistance to various drugs and to form strong biofilms, which makes it necessary to develop new antibacterial drugs. The essential oil of Melaleuca alternifolia is used as an antibacterial, a property believed to be mainly due to the presence of terpinen-4-ol. Based on this, the objective of this study was to evaluate the antibacterial and antibiofilm potential of terpinen-4-ol against S. aureus. The Minimal Inhibitory and Minimal Bactericidal Concentrations (MIC and MBC) of terpinen-4-ol were determined, and the effect of its combination with antibacterial drugs as well as its activity against S. aureus biofilms were evaluated. In addition, an in silico analysis of its pharmacokinetic parameters and a molecular docking analysis were performed. Terpinen-4-ol presented a MIC of 0.25% (v/v) and an MBC of 0.5% (v/v) (bactericidal action); its association with antibacterials was also effective. Terpinen-4-ol has good antibiofilm activity, and the in silico results indicated adequate absorption and distribution of the molecule in vivo. Molecular docking indicated that penicillin-binding protein 2a is a possible target of terpinen-4-ol in S. aureus. This work highlights the good potential of terpinen-4-ol as an antibacterial product and provides support for future pharmacological studies of this molecule, aiming at its therapeutic application.

Isoeugenol and Hybrid Acetamides against Candida albicans Isolated from the Oral Cavity

“…The isoeugenol and nystatin interaction was evaluated according to the checkerboard methodology, which is an in vitro laboratory technique that allows the interaction of two or more molecules through the construction of a two-dimensional matrix between the tested substances [ 31 ]. The data obtained in this study demonstrated that the interaction of isoeugenol with nystatin was indifferent, with index values fractional inhibitory concentration (FIC) = 3.09 and FIC = 2.10, for C. albicans LM-4b and C. albicans ATCC-76485, respectively ( Table 3 ).…”

“…The tests were performed in triplicate. The MFC/MIC ratio was calculated to determine the fungicidal (MFC/MIC < 4) or fungistatic (MFC/MIC ≥ 4) action of the products [ 31 , 40 ].…”

“…Then, 50 µL of isoeugenol at MIC/8, MIC/4, MIC/2, MIC, MIC × 2, MIC × 4 and MIC × 8 concentrations were added vertically and 50 µL of nystatin, at these same concentrations, were added horizontally. Finally, the fungal inoculum of C. albicans LM-4b and ATCC 76485 was added to the wells and the covered plates were incubated at 35 °C ± 2 °C for 72 h [ 31 , 47 ]. Controls of sterility of the medium and viability of the strains were performed.…”

“…The FIC A , in turn, was determined by the division of the combined MIC A /MIC A alone and the FIC B determined by the division of the combined MIC B /MIC B alone. The results were interpreted as follows: synergism (FICI ≤ 0.5), indifference (0.5 ≥ FICI < 4) and antagonism (FICI ≥ 4) [ 31 , 47 ].…”

Integration of Metabolomics and Transcriptomics Indicates Changes in MRSA Exposed to Terpinen-4-ol

“…Terpinen-4-ol was considered to be the main active ingredient of TTO [6], and ISO 4730-2017 stipulates that the content of terpinen-4-ol should not be less than 30% [8]. But there were few studies about the strong antibio lm activity [9] of terpinen-4-ol, and its mechanism was not yet fully understood.…”