Hydroxytyrosol (HT) analogues act as potent antifungals by direct disruption of the fungal cell membrane

Abstract

Key words: fungal pathogens/Aspergillus nidulans/plasma membrane/antimicrobial/resistance Fungal infections constitute an emerging threat and a prevalent health problem due to increasing number of immunocompromised people and pharmacological or other treatments aiming at viral infections, cancer or allergies. Currently used antifungals suffer from inefficiency, toxic side effects and developing drug-resistance. Additionally, over the last two decades no new classes of antifungals have been approved, emphasizing the urgent need for developing a novel generation of antifungals. Here we investigate the antifungal activity of a series of chemically synthesized Hydroxytyrosol (HT) analogues. ΗΤ is one of the major phenolic compounds in olive oil, shown to possess radical-scavenging antioxidant, antiproliferative, proapoptotic and anti-inflammatory activities. No previous report has studied HT analogues as antifungals. We show that specific analogues have broad and strong antifungal activity, significantly stronger than the parent compound HT. Using A. nidulans as an in vivo cellular model system, we show that antifungal HT analogues have an unprecedented efficiency in fungal plasma membrane destruction. Importantly, antifungal HT analogues did not show toxicity in a mammalian cell line, whereas no resistance to HT analogues was obtained by standard mutagenesis. Our results open the way for the development of a novel, efficient and safer class of antifungals.

Circular bioeconomy in strawberry cultivation: phytochemicals in fruits and leaves, and yield potential of seven genotypes

“…Analysis of the phenolic profile showed the presence of higher levels of 3-hydroxytyrosol, catechin, and rutin in 'Fronteras' leaves (Table 4), compounds with free radical scavenger properties and important phytotherapeutic properties. The 3-hydroxytyrosol, a phenylethanoid, has been described to inhibit the growth of disease-inducing fungi and bacteria (Diallinas et al 2018), and is described to occur at higher levels in olives (fruits and leaves). Although the content in strawberry leaves is lower than that described in olive trees, the identification of this compound could be an indication of its possible use in biotechnological processes, including pharmacological ones.…”

Hydroxytyrosol (HT) Analogs Act as Potent Antifungals by Direct Disruption of the Fungal Cell Membrane

“…This work has been released as a pre-print at BioRxiv ( Diallinas et al, 2018 ). We thank Dr. Joseph Meletiadis, Assistant Professor of Microbiology in the Medical School of University of Athens, for Amphotericin B and Michalis Papadourakis for help in preliminary uptake experiments.…”