Antifungal activity of eicosanoic acids isolated from the endophytic fungus Mycosphaerella sp. against Cryptococcus neoformans and C. gattii.
The antifungal effects of two eicosanoic acids, 2-amino-3,4-dihydroxy-2-25-(hydroxymethyl)-14-oxo-6,12-eicosenoic acid (compound 1) and myriocin (compound 2), isolated from Mycosphaerella sp. were evaluated against Cryptococcus neoformans and C. gattii. The compounds displayed antifungal activities against several isolates of C. neoformans and C. gattii, with minimal inhibitory concentration (MIC) values ranging from 0.49 to 7.82 μM for compound 1 and 0.48-1.95 μM for compound 2. In the checkerboard microtiter test, both compounds exhibited synergistic activity with amphotericin B against C. gattii. Ultrastructural analysis revealed several signs of damage in C. gattii and C. neoformans cells treated with compounds 1 and 2, including deformities in cell shape, depressions on the surface, and withered cells. The cells of C. gattii treated with compounds 1 and 2 showed less loss of cellular material in comparison to those treated with amphotericin B. The difference in cellular material loss increased in a test compound concentration-dependent manner. Consistent with this observation, compounds 1 and 2 were able to internalize propidium iodide (PI) in C. gattii cells. In addition, compound 2 induced the formation of several pseudohyphae, suggesting that it could reduce virulence in C. gattii cells. The study results show that these natural products led to membrane damage; however, this may not be the main target of action. These compounds have potential antifungal activity and could be useful in further studies for developing more effective combination therapies with amphotericin B and reducing side effects in patients.
Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil; Laboratório de Química de Produtos Naturais Bioativos, Centro de Pesquisa René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, MG, Brazil.
Cristiane Bigatti
CB
Pereira
Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
Nívea
N
Pereira de Sá
Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
Beatriz Martins
BM
Borelli
Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
Carlos Augusto
CA
Rosa
Departamento de Química, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
Paulo Jorge Sanches
PJS
Barbeira
Laboratório de Química de Produtos Naturais Bioativos, Centro de Pesquisa René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, MG, Brazil.
Betania Barros
BB
Cota
Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil. Electronic address: sjohann@icb.ufmg.br.
Susana
S
Johann
D000666:Amphotericin B / Q000494:pharmacology; D000935:Antifungal Agents / Q000302:isolation & purification / Q000494:pharmacology*; D001203:Ascomycota / Q000737:chemistry*; D001688:Biological Products / Q000302:isolation & purification / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000648:ultrastructure; D056285:Cryptococcus gattii / Q000166:cytology / Q000187:drug effects*; D003455:Cryptococcus neoformans / Q000166:cytology / Q000187:drug effects*; D004357:Drug Synergism; D004537:Eicosanoic Acids / Q000302:isolation & purification / Q000494:pharmacology*; D060026:Endophytes / Q000737:chemistry*; D008826:Microbial Sensitivity Tests
D000935:Antifungal Agents; D001688:Biological Products; D004537:Eicosanoic Acids; D000666:Amphotericin B
Cryptococcus; Membrane damage; Mycosphaerella; Synergism