Endophytic fungal compounds active against Cryptococcus neoformans and C. gattii

Abstract

Infections with Cryptococcus are invasive mycoses associated with significant morbidity and mortality, mainly in immunosuppressed patients. Several drugs have been introduced to combat these opportunistic infections. However, resistance of this organism to antifungal drugs has increased, causing difficulties in the treatment. The goal of this work was to evaluate the antifungal activity of ethanol extracts from endophytic fungi isolated from plants collected from different Brazilian ecosystems and to perform the fractionation of the most promising extract. Four-hundred fungal extracts were investigated by microdilution broth assays against Cryptococcus neoformans and Cryptococcus gattii at a concentration of 500 μg ml(-1). Among them, the extract of Mycosphaerella sp. UFMGCB 2032, an endophytic fungus isolated from the plant Eugenia bimarginata DC. (Myrtaceae) exhibited outstanding antifungal activity against C. neoformans and C. gattii, with MIC values of 31.2 μg ml(-1) and 7.8 μg ml(-1), respectively. The fractionation of this extract using liquid-liquid partitioning and semi-preparative HPLC afforded two eicosanoic acids with antifungal activity, compound 1, (2S,3R,4R)-(E)-2-amino-3,4-dihydroxy-2-(hydroxymethyl)-14-oxoeicos-6,12-dienoic acid with MIC values ranging from 1.3-2.50 μg ml(-1), and compound 2, known as myriocin, with MIC values of 0.5 μg ml(-1) against C. neoformans and C. gattii. These compounds are reported for the first time in the Mycosphaerella genus.

Antifungal Agents in Agriculture: Friends and Foes of Public Health

“…Xylaria spp., associated with the Azadirachta indica plant from China, are a source of new bioactive compounds, some of which exhibit relevant pharmacological properties for drug discovery [141], presenting with antifungal activities against C. albicans, Aspergillus niger, and Fusarium avenaceum [127,142]. The fungus Mycosphaerella, which is an endophyte of the plant Eugenia bimarginata from Brazil, has been shown to produce two eicosanoid acids that have antifungal activities against C. neoformans and C. gattii [143]. The cryptocandin lipopeptide is isolated from the fungus Cryptosporiopsis quercina, which grows in wood species in Europe.…”

“…[141] Azadirachta indica [127,142] Bioactive compounds [141] C. albicans Aspergillus niger Fusarium avenaceum [127,142] Mycosphaerella spp. [143] Eugenia bimarginata [143] Eicosanoid acids [143] Cryptococcus neoformans C. gattii [143] Cryptosporiopsis quercina [144] Wood species in Europe [144] Cryptocandin lipopeptide [144] Botrytis cinerea [144] Novel molecular biology approaches have been used for the identification and characterization of genetic elements and metabolites involved in the interactions between plants and endophytic microorganisms [146]. For these endophytic microorganisms to be marketed as successful biocontrol agents, certain criteria must be met regarding their ease of application and dissemination to crops without causing any off-target effects.…”

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“…1S-27S, Supporting Information) in order to verify if the published identifications are correct or if there are misidentified species. Based on these analyses, we noticed that two isolates were erroneously identified at the genus level in the previous articles: Pereira et al [29] identified the strain UFMGCB2032 (Genbank code KF681521), isolated from Eugenia bimarginata, as Mycosphaerella sp. based on phylogenetic analysis.…”

“…(Fig. 17S) Mycosphaerella was divided into several genera, and the isolate belongs to the genus Phaeophleospora [29] Baccharis trimera UFMGCB4425 KJ404206 Alternaria sp. Alternaria sp.…”

“…Pereira et al [29] worked with 400 endophytic fungi isolated from different Brazilian ecosystems in order to select active strains against of Cryptococcus neoformans and Cryptococcus gattii. Strain Mycosphaerella sp.…”