Control of human and plant fungal pathogens using pentaene macrolide 32, 33-didehydroroflamycoin.

AIMS: The aim of this study was to address the toxicity of recently described polyene macrolide 32, 33-didehydroroflamycoin (DDHR) on a wide range of fungal pathogens and its potential to control plant fungal diseases. METHODS AND RESULTS: The antifungal activity of DDHR in vitro was examined against common human and plant pathogenic fungi using a broth microdilution assay and a disk diffusion assay. Minimum inhibitory concentrations ranged from 12·5 to 35 µg ml(-1) . A radial growth inhibition assay showed that DDHR inhibited mycelia growth, inducing mycelial necrosis and affecting sporulation. During the in vivo assay on apple fruits administration of DDHR 1 h before fungal inoculation inhibited spreading of the infection. Importantly, DDHR exhibited no phytotoxic effects on the model plant, Capsicum annum, verified by the plant growth rate and chlorophyll content. CONCLUSIONS: DDHR inhibits growth of various plant pathogens in vitro with the strongest activity against Alternaria alternata, Colletotrichum acutatum and Penicillium expansum, and protects apple fruits from decay. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report of the inhibitory effect of DDHR on important pathogenic fungal isolates. DDHR could be a good scaffold for developing new antifungal agents for fruit and vegetable protection.

In vitro antifungal activities of amphotericin B, 5-fluorocytosine, fluconazole and itraconazole against Cryptococcus neoformans isolated from cerebrospinal fluid and blood from patients in Serbia.

Recently, geographic variations in resistance to agents commonly used in the treatment of cryptococcosis have been reported. Therefore, the antifungal susceptibilities of 31 clinical isolates of Cryptococcus neoformans, collected in Serbia during 10-year period, were investigated. Strains were isolated from cerebrospinal fluid (n=28) and blood (n=3), from patients with AIDS (n=26), lymphoma (n=4) and kidney transplant recipient (n=1). The minimal inhibitory concentrations (MICs) of amphotericin B, 5-fluorocytosine, fluconazole and itraconazole were determined by the E-test(®) method. The isolates were highly susceptible to amphotericin B (100% susceptibility at MIC<0.5 µg/mL) and 5-fluorocytosine (87.1% susceptibility at MIC ≤ 4 µg/mL). Geometric mean MIC of amphotericin B and 5-fluorocytosine were 0.102 µg/mL and 0.396 µg/mL, respectively. Fluconazole exhibited the lowest activity in vitro (48.4% susceptibility at MIC ≤ 8 µg/mL) with a significant resistance rate. The activity of itraconazole was also decreased (48.4% susceptibility at MIC ≤ 0.25 µg/mL). The geometric mean MIC of fluconazole stood at 15.14 µg/mL and of itraconazole was 0.144 µg/mL. Cross-resistance among azoles was not common (3.2%), but the parallel increase in fluconazole and itraconazole MIC has been observed (P<0.01). The low rate of susceptibility to fluconazole stresses the need for active antifungal surveillance of C. neoformans and of the corresponding data from different geographic regions.