Antifungal activity of eicosanoic acids isolated from the endophytic fungus Mycosphaerella sp against Cryptococcus neoformans and C-gattii

作者：Pereira Cristiane Bigatti; de Sa Nivea Pereira; Borelli Beatriz Martins; Rosa Carlos Augusto; Sanches Barbeira Paulo Jorge; Cota Betania Barros; Johann Susana

来源：Microbial Pathogenesis, 2016, 100: 205-212.

DOI：10.1016/j.micpath.2016.09.022

• Mycosphaerella
• Cryptococcus
• Membrane damage
• Synergism

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 mu M for compound 1 and 0.48-1.95 mu M 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.

• 出版日期2016-11