Abstract
BackgroundThe continuous emergence of multidrug-resistant (MDR) bacteria drastically reduced the efficacy of our antibiotic armory and consequently, increased the frequency of therapeutic failure. The search for bioactive constituents from endophytic fungi against MDR bacteria became a necessity for alternative and promising strategies, and for the development of novel therapeutic solutions. We report here the isolation and structure elucidation of antibacterial and cytotoxic compounds from Phomopsis sp., an endophytic fungus associated with Garcinia kola nuts.MethodsThe fungus Phomopsis sp. was isolated from the nut of Garcinia kola. The crude extract was prepared from mycelium of Phomopsis sp. by maceration in ethyl acetate and sequentially fractionated by column chromatography. The structures of isolated compounds were elucidated on the basis of spectral studies and comparison with published data. The isolated compounds were evaluated for their antibacterial and anticancer properties by broth microdilution and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide methods respectively. The samples were also tested spectrophotometrically for their hemolytic properties against human red blood cells.ResultsThe fractionation of the crude extract afforded three known cytochalasins including 18-metoxycytochalasin J (1), cytochalasins H (2) and J (3) together with alternariol (4). The cytochalasin compounds showed different degrees of antibacterial activities against the tested bacterial pathogens. Shigella flexneri was the most sensitive microorganism while Vibrio cholerae SG24 and Vibrio cholerae PC2 were the most resistant. Ampicillin did not show any antibacterial activity against Vibrio cholerae NB2, Vibrio cholerae PC2 and Shigella flexneri at concentrations up to 512 μg/mL, but interestingly, these multi-drug resistant bacterial strains were sensitive to the cytochalasin metabolites. These compounds also showed significant cytotoxic properties against human cancer cells (LC50 = 3.66–35.69 μg/mL) with low toxicity to normal non-cancer cells.ConclusionThe three cytochalasin compounds isolated from the Phomopsis sp. crude extract could be a clinically useful alternative for the treatment of cervical cancer and severe infections caused by MDR Shigella and Vibrio cholerae.
Highlights
The continuous emergence of multidrug-resistant (MDR) bacteria drastically reduced the efficacy of our antibiotic armory and increased the frequency of therapeutic failure
Following the application of the OSMAC principle, we found out that when the culture conditions were changed from potato dextrose agar (PDA) medium to solid state medium, fermentation significantly changed and based on high-performance liquid chromatography (HPLC) monitoring, 18-metoxycytochalasin J (1), cytochalasins H (2) and J (3) and alternariol (4) were isolated
We evaluate the cytotoxic activities of cytochalasins against bacterial species and human cervical cancer cell lines, with emphasis on MDR Shigella flexneri and Vibrio cholerae
Summary
The continuous emergence of multidrug-resistant (MDR) bacteria drastically reduced the efficacy of our antibiotic armory and increased the frequency of therapeutic failure. As one of the most frequently isolated secondary metabolites from endophytic fungi cultures, cytochalasins are produced by Phoma [5], Hormiscium [6], Helminthosporium [7], Phomopsis [8] and Curualuriu [9] genera. They have been identified as contaminants of potato [5], tomato [6], pecan [10], rice [11], millet [8] and litchi fruit [9]. Most works on endophytic fungi have been centered on plants in the temperate and tropical regions of the world [18]
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