Bio-inspired design of antimicrobial synergistic mixtures

Abstract

Microbial infections are becoming more common and more severe while the development of new antimicrobials stagnates. Antimicrobial potential of aromatic plants has been recognized since antiquity and is mainly attributed to their chemically diverse volatile organic compounds (VOCs) [1 – 2]. Inspired by plant defenses, we undertook to look for antimicrobial mixtures encompassing VOCs. Initially, thirty two essential oils (EOs) were analysed by GC/MS and NMR and their antimicrobial activity was measured on several bacteria, yeasts and filamentous fungi. The objectives were to find antimicrobial oils, to understand their antimicrobial potential, to study their mode of action, and eventually discover synergistic antimicrobial preparations. For example, Juniperus excelsa M. Bieb. EOs were antibacterial (MIC Staphylococcus aureus 64 – 128 µg/ml) while their main components α-pinene, α-cedrol and δ-3-carene were inactive (MIC > 512 µg/ml). A synthetic essential oil was reconstituted mixing these compounds. This synthetic EO showed some activity (MIC 256 µg/ml) suggesting a synergy between the EO components. It was also found that Hirtellina lobelii (DC.) Dittrich EO, rich in α-bisabolol, was antifungal by disrupting fungal membrane and ultimately lysing cells (Fig. 1). We hypothesized that this EO could increase drug cell penetration, and interestingly, it demonstrated synergistic interactions with antifungal drugs, more particularly with fluconazole and griseofulvin (FICI 0.2 – 0.3). In topical applications, these combinations would reduce the possible side effects of current therapies by decreasing the dose of drug and the amount of EO. Altogether, these results lead us to believe that plant defense arsenal can inspire alternative ways of addressing the societal issue of multi-drug resistant infections.