Hydroxytyrosol (HT) Analogs Act as Potent Antifungals by Direct Disruption of the Fungal Cell Membrane
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 dev...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-11-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fmicb.2018.02624/full |
| _version_ | 1811227478955393024 |
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| author | George Diallinas Nausica Rafailidou Ioanna Kalpaktsi Aikaterini Christina Komianou Vivian Tsouvali Iliana Zantza Emmanuel Mikros Alexios Leandros Skaltsounis Ioannis K. Kostakis |
| author_facet | George Diallinas Nausica Rafailidou Ioanna Kalpaktsi Aikaterini Christina Komianou Vivian Tsouvali Iliana Zantza Emmanuel Mikros Alexios Leandros Skaltsounis Ioannis K. Kostakis |
| author_sort | George Diallinas |
| collection | DOAJ |
| description | 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) analogs. HT 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 analogs as antifungals. We show that specific analogs have broad and strong antifungal activity, significantly stronger than the parent compound HT. Using Aspergillus nidulans as an in vivo cellular model system, we show that antifungal HT analogs have an unprecedented efficiency in fungal plasma membrane destruction. Importantly, antifungal HT analogs did not show toxicity in a mammalian cell line, whereas no resistance to HT analogs was obtained by standard mutagenesis. Our results open the way for the development of a novel, efficient and safer class of antifungals. |
| first_indexed | 2024-04-12T09:42:11Z |
| format | Article |
| id | doaj.art-4cd442cd8b0444c6bc695bb492a98e06 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-04-12T09:42:11Z |
| publishDate | 2018-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-4cd442cd8b0444c6bc695bb492a98e062022-12-22T03:38:02ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2018-11-01910.3389/fmicb.2018.02624409963Hydroxytyrosol (HT) Analogs Act as Potent Antifungals by Direct Disruption of the Fungal Cell MembraneGeorge Diallinas0Nausica Rafailidou1Ioanna Kalpaktsi2Aikaterini Christina Komianou3Vivian Tsouvali4Iliana Zantza5Emmanuel Mikros6Alexios Leandros Skaltsounis7Ioannis K. Kostakis8Department of Biology, National and Kapodistrian University of Athens, Athens, GreeceDepartment of Biology, National and Kapodistrian University of Athens, Athens, GreeceDepartment of Pharmacy, National and Kapodistrian University of Athens, Athens, GreeceDepartment of Pharmacy, National and Kapodistrian University of Athens, Athens, GreeceDepartment of Biology, National and Kapodistrian University of Athens, Athens, GreeceDepartment of Pharmacy, National and Kapodistrian University of Athens, Athens, GreeceDepartment of Pharmacy, National and Kapodistrian University of Athens, Athens, GreeceDepartment of Pharmacy, National and Kapodistrian University of Athens, Athens, GreeceDepartment of Pharmacy, National and Kapodistrian University of Athens, Athens, GreeceFungal 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) analogs. HT 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 analogs as antifungals. We show that specific analogs have broad and strong antifungal activity, significantly stronger than the parent compound HT. Using Aspergillus nidulans as an in vivo cellular model system, we show that antifungal HT analogs have an unprecedented efficiency in fungal plasma membrane destruction. Importantly, antifungal HT analogs did not show toxicity in a mammalian cell line, whereas no resistance to HT analogs was obtained by standard mutagenesis. Our results open the way for the development of a novel, efficient and safer class of antifungals.https://www.frontiersin.org/article/10.3389/fmicb.2018.02624/fullfungal pathogensAspergillus nidulansplasma membraneantimicrobialresistance |
| spellingShingle | George Diallinas Nausica Rafailidou Ioanna Kalpaktsi Aikaterini Christina Komianou Vivian Tsouvali Iliana Zantza Emmanuel Mikros Alexios Leandros Skaltsounis Ioannis K. Kostakis Hydroxytyrosol (HT) Analogs Act as Potent Antifungals by Direct Disruption of the Fungal Cell Membrane Frontiers in Microbiology fungal pathogens Aspergillus nidulans plasma membrane antimicrobial resistance |
| title | Hydroxytyrosol (HT) Analogs Act as Potent Antifungals by Direct Disruption of the Fungal Cell Membrane |
| title_full | Hydroxytyrosol (HT) Analogs Act as Potent Antifungals by Direct Disruption of the Fungal Cell Membrane |
| title_fullStr | Hydroxytyrosol (HT) Analogs Act as Potent Antifungals by Direct Disruption of the Fungal Cell Membrane |
| title_full_unstemmed | Hydroxytyrosol (HT) Analogs Act as Potent Antifungals by Direct Disruption of the Fungal Cell Membrane |
| title_short | Hydroxytyrosol (HT) Analogs Act as Potent Antifungals by Direct Disruption of the Fungal Cell Membrane |
| title_sort | hydroxytyrosol ht analogs act as potent antifungals by direct disruption of the fungal cell membrane |
| topic | fungal pathogens Aspergillus nidulans plasma membrane antimicrobial resistance |
| url | https://www.frontiersin.org/article/10.3389/fmicb.2018.02624/full |
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