Fungal Biofilms as a Valuable Target for the Discovery of Natural Products That Cope with the Resistance of Medically Important Fungi-Latest Findings.

Estefanía Butassi,María Cecilia Carpinella,Laura Svetaz,Thomas Efferth,Susana Zacchino

doi:10.3390/antibiotics10091053

Abstract

The development of new antifungal agents that target biofilms is an urgent need. Natural products, mainly from the plant kingdom, represent an invaluable source of these entities. The present review provides an update (2017–May 2021) on the available information on essential oils, propolis, extracts from plants, algae, lichens and microorganisms, compounds from different natural sources and nanosystems containing natural products with the capacity to in vitro or in vivo modulate fungal biofilms. The search yielded 42 articles; seven involved essential oils, two Brazilian propolis, six plant extracts and one of each, extracts from lichens and algae/cyanobacteria. Twenty articles deal with the antibiofilm effect of pure natural compounds, with 10 of them including studies of the mechanism of action and five dealing with natural compounds included in nanosystems. Thirty-seven manuscripts evaluated Candida spp. biofilms and two tested Fusarium and Cryptococcus spp. Only one manuscript involved Aspergillus fumigatus. From the data presented here, it is clear that the search of natural products with activity against fungal biofilms has been a highly active area of research in recent years. However, it also reveals the necessity of deepening the studies by (i) evaluating the effect of natural products on biofilms formed by the newly emerged and worrisome health-care associated fungi, C. auris, as well as on other non-albicans Candida spp., Cryptococcus sp. and filamentous fungi; (ii) elucidating the mechanisms of action of the most active natural products; (iii) increasing the in vivo testing.

Highlights

In recent decades, fungi has emerged as a major cause of life-threatening invasive human infections, in particular among immunocompromised patients [1,2,3], those with human immunodeficiency virus (HIV), cancer patients receiving chemotherapy, transplant recipients, extremely aged persons and subjects in intensive care units [4,5].Fungal infections lead to mortalities estimated in 1.5 million per year, having a great impact on global human health [5]
The natural products that demonstrated activity against fungal biofilms from 2017 to May 2021 were collected, with the aim of offering an overview of the progress made in this area to curb difficult-to-eradicate fungal infections
The type of natural products that showed better antibiofilm activities, the fungal species of the target biofilms, the type of assays used and the mechanisms of action were analyzed in order to detect the advances performed in this period that can be the basis of future works

Summary

Introduction

Fungi has emerged as a major cause of life-threatening invasive human infections, in particular among immunocompromised patients [1,2,3], those with human immunodeficiency virus (HIV), cancer patients receiving chemotherapy, transplant recipients, extremely aged persons and subjects in intensive care units [4,5].Fungal infections lead to mortalities estimated in 1.5 million per year, having a great impact on global human health [5]. Fungi has emerged as a major cause of life-threatening invasive human infections, in particular among immunocompromised patients [1,2,3], those with human immunodeficiency virus (HIV), cancer patients receiving chemotherapy, transplant recipients, extremely aged persons and subjects in intensive care units [4,5]. Most Common Etiological Agents Causing Fungal Infections. The most common fungi identified in systemic infections are the yeasts of the Candida and Cryptococcus genera, as well as the filamentous fungi of the Aspergillus genus [6,7,8]. Among Candida spp., C. albicans showed to be the fourth most common cause of nosocomial bloodstream infections [10], a recent global shift in epidemiology towards non-albicans Candida spp., such as C. glabrata, C. parapsilopsis, C. tropicalis, C. krusei and lastly, C. auris, has been detected [11,12]. Apart from the mentioned fungi, other species such as Pneumocystis jirovecii, Histoplasma capsulatum and the mucormycetes of Mucor, Absidia and Rhizopus genera, are important fungal pathogens responsible for the majority of serious fungal diseases [13,14,15]

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