Sphaerostilbellins, New Antimicrobial Aminolipopeptide Peptaibiotics from Sphaerostilbella toxica

Sphaerostilbella toxica is a mycoparasitic fungus that can be found parasitizing wood-decay basidiomycetes in the southern USA. Organic solvent extracts of fermented strains of S. toxica exhibited potent antimicrobial activity, including potent growth inhibition of human pathogenic yeasts Candida albicans and Cryptococcus neoformans, the respiratory pathogenic fungus Aspergillus fumigatus, and the Gram-positive bacterium Staphylococcus aureus. Bioassay-guided separations led to the purification and structure elucidation of new peptaibiotics designated as sphaerostilbellins A and B. Their structures were established mainly by analysis of NMR and HRMS data, verification of amino acid composition by Marfey’s method, and by comparison with published data of known compounds. They incorporate intriguing structural features, including an N-terminal 2-methyl-3-oxo-tetradecanoyl (MOTDA) residue and a C-terminal putrescine residue. The minimal inhibitory concentrations for sphaerostilbellins A and B were measured as 2 μM each for C. neoformans, 1 μM each for A. fumigatus, and 4 and 2 μM, respectively, for C. albicans. Murine macrophage cells were unaffected at these concentrations

Antibiosis Levels Of Common Bean Genotypes Toward Zabrotes Subfasciatus (boheman) (coleoptera: Bruchidae) And Its Correlation With Flavonoids

Expression of the antibiosis-resistance category to weevils has been evaluated in several bean genotypes with very promising results. Among the several causes responsible for this resistance category the arcelin protein and trypsin inhibitors stand out. Other mechanisms may be associated with plant resistance to the attack of weevils; however, few studies seek to discover these possible causes. Thus, our research aimed at identifying bean genotypes resistant to Zabrotes subfasciatus, classify them into resistance levels, quantify the content of flavonoids, and correlate it with data obtained from the genotypes. An antibiosis test was performed with beans of 43 genotypes and 40 replications (bean grains) under a completely randomized design. The biological parameters recorded from Z. subfasciatus were the periods from egg to larvae, larvae to adult, egg to adult, longevity and life cycle, in addition to egg viability, adults emerged, susceptibility relative index, adult weight, sex ratio, and the dry mass consumed by larvae. The chemical profile of flavonoids from each genotype was assessed by means of LC-MS. Based on the results of the weevil biological parameters and dry mass consumed provided by univariate and multivariate statistical analyses, the bean genotypes were classified into four levels of resistance (antibiosis): highly resistant, moderately resistant, susceptible and highly susceptible. Among the evaluated flavonoids, we could identify isoquercitrin; however, it has no correlation with the expression of resistance. From the results obtained in this work, more studies will be conducted with the genotypes that stood out as resistant, evaluating other resistance categories and defense mechanisms of these materials against the attack of Z. subfasciatus and other pests, as well as studies of other important agronomic characteristics aiming at future commercialization of the bean genotypes. © 2016 Elsevier Ltd.67637

Campafungins: Inhibitors of Candida albicans and Cryptococcus neoformans Hyphal Growth.

Campafungin A is a polyketide that was recognized in the Candida albicans fitness test due to its antiproliferative and antihyphal activity. Its mode of action was hypothesized to involve inhibition of a cAMP-dependent PKA pathway. The originally proposed structure appeared to require a polyketide assembled in a somewhat unusual fashion. However, structural characterization data were never formally published. This background stimulated a reinvestigation in which campafungin A and three closely related minor constituents were purified from fermentations of a strain of the ascomycete fungus Plenodomus enteroleucus. Labeling studies, along with extensive NMR analysis, enabled assignment of a revised structure consistent with conventional polyketide synthetic machinery. The structure elucidation of campafungin A and new analogues encountered in this study, designated here as campafungins B, C, and D, is presented, along with a proposed biosynthetic route. The antimicrobial spectrum was expanded to methicillin-resistant Staphylococcus aureus, Candida tropicalis, Candida glabrata, Cryptococcus neoformans, Aspergillus fumigatus, and Schizosaccharomyces pombe, with MICs ranging as low as 4-8 μg mL-1 in C. neoformans. Mode-of-action studies employing libraries of C. neoformans mutants indicated that multiple pathways were affected, but mutants in PKA/cAMP pathways were unaffected, indicating that the mode of action was distinct from that observed in C. albicans