Abstract
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.
Highlights
Cryptococcus species are among the most common causes of invasive fungal infections globally
Current treatments are limited to few antifungal agents, with no new therapies introduced in recent decades
We explored the antifungal spectrum of these new SpterpatinaisbiToTtiIc-s0.467 (=NRRL 66953) and DPL-12808 (=NRRL 66954) of S. toxica from Texas, USA have been described previously [8]
Summary
Cryptococcus species are among the most common causes of invasive fungal infections globally. Current treatments are limited to few antifungal agents (amphotericin B, flucytosine, fluconazole), with no new therapies introduced in recent decades. These therapeutics remain unsatisfactory because of their toxicity, inability to reliably eradicate the fungal pathogen and the emergence of drug resistance [3,4]. FBoeusniddesclsapssecoifesnoatfuSrpahl aperroosdtuilcbtesllaof[8t]h,etsheeffuanmgiilyarHe yppeopctareibaicoetaicesi,ninclculuddesinwgepllepkntaoibwonlsm, tyhcaotpmaeradsiiattiec t(halesior mknyocwopnaarassfiutengliifceosltoyules)[g16e–n1e9r]a., e.g., Trichoderma, Hypomyces, and Escovopsis [9,10,11] All fungi in this fHamerielyins,tuwdeiepdrotoviddaetedhetaavielsboenenthsheofwernmteonhtaatvioena ocof mS.ptleoxxicsaecloenaddainrgy mtoettahbeobliisomacwtivhiitcyh-ginuipdaerdt pcounritfriicbautitoens taontdhsetirruccatpuarecietylutcoidiantvioandeo,fkniellw, apnedpctaoilboinoitzicesowthitehr afunnugniu[1su2–a1l 5N].-tTerhme imnaolsftacttoynasicsitdenantldy Cfo-utenrdmcinlaasls pouf tnreastucirnael prerosidduucet.s Fouf rtthheesremfuorneg,iwaree epxeppltoariebdiottihces, ainnctilfuudnignagl pseppetcatribuomls,otfhatht emseednieawte ptheepitramibyioctoipcsa.rasite life style [16,17,18,19]
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