title: 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.
authors.affiliation: Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Cristiane B
authors.initials: CB
authors.lastname: Pereira
authors.affiliation: Departamento de Química e Exatas, Universidade Estadual do Sudoeste da Bahia, Campus Universitário de Jequié, Jequié, Bahia, Brazil.
authors.forename: Djalma M
authors.initials: DM
authors.lastname: de Oliveira
authors.affiliation: Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Alice Fs
authors.initials: AF
authors.lastname: Hughes
authors.affiliation: Laboratório de Química de Produtos Naturais, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, MG, Brazil.
authors.forename: Markus
authors.initials: M
authors.lastname: Kohlhoff
authors.affiliation: Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Mariana
authors.initials: M
authors.lastname: LA Vieira
authors.affiliation: Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Aline B
authors.initials: AB
authors.lastname: Martins Vaz
authors.affiliation: Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Mariana C
authors.initials: MC
authors.lastname: Ferreira
authors.affiliation: Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Camila R
authors.initials: CR
authors.lastname: Carvalho
authors.affiliation: Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Luiz H
authors.initials: LH
authors.lastname: Rosa
authors.affiliation: Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Rosa
authors.affiliation: Laboratório de Química de Produtos Naturais, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, MG, Brazil.
authors.forename: Tânia Ma
authors.initials: TM
authors.lastname: Alves
authors.affiliation: Laboratório de Química de Produtos Naturais, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, MG, Brazil.
authors.forename: Carlos L
authors.initials: CL
authors.lastname: Zani
authors.affiliation: Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Susana
authors.initials: S
authors.lastname: Johann
authors.affiliation: Laboratório de Química de Produtos Naturais, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, MG, Brazil.
authors.forename: Betania B
authors.initials: BB
authors.lastname: Cota
mesh_terms: D000935:Antifungal Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001938:Brazil; D016000:Cluster Analysis; D056285:Cryptococcus gattii / Q000187:drug effects*; D003455:Cryptococcus neoformans / Q000187:drug effects*; D004271:DNA, Fungal / Q000737:chemistry / Q000235:genetics; D060026:Endophytes / Q000737:chemistry* / Q000145:classification / Q000235:genetics / Q000302:isolation & purification; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010802:Phylogeny; D010944:Plants / Q000382:microbiology; D017422:Sequence Analysis, DNA
chemical_list: D000935:Antifungal Agents; D004271:DNA, Fungal