Soil fungi are known to contain a rich variety of defense metabolites that allow them to compete with other organisms (fungi, bacteria, nematodes, and insects) and help them occupy more preferential areas at the expense of effective antagonism. These compounds possess antibiotic activity towards a wide range of other microbes, particularly fungi that belong to different taxonomical units. These compounds include peptaibols, which are non-ribosomal synthesized polypeptides containing non-standard amino acid residues (alpha-aminoisobutyric acid mandatory) and some posttranslational modifications. We isolated a novel antibiotic peptide from the culture medium of Emericellopsis alkalina, an alkalophilic strain. This peptide, called emericellipsin A, exhibited a strong antifungal effect against the yeast Candida albicans, the mold fungus Aspergillus niger, and human pathogen clinical isolates. It also exhibited antimicrobial activity against some Gram-positive and Gram-negative bacteria. Additionally, emericellipsin A showed a significant cytotoxic effect and was highly active against Hep G2 and HeLa tumor cell lines. We used NMR spectroscopy to reveal that this peptaibol is nine amino acid residues long and contains non-standard amino acids. The mode of molecular action of emericellipsin A is most likely associated with its effects on the membranes of cells. Emericellipsin A is rather short peptaibol and could be useful for the development of antifungal, antibacterial, or anti-tumor remedies.

Novel antimicrobial peptides with antifungal and cytotoxic activity were derived from the alkalophilic fungus Emericellopsis alkalina VKPM F1428. We previously reported that this strain produced emericellipsin A (EmiA), which has strong antifungal and cytotoxic properties. Further analyses of the metabolites obtained under a special alkaline medium resulted in the isolation of four new homologous (Emi B–E). In this work, we report the complete primary structure and detailed biological activity for the newly synthesized nonribosomal antimicrobial peptides called emericellipsins B–E. The inhibitory activity of themajor compound, EmiA, against drug-resistant pathogenic fungi was similar to that of amphotericin B (AmpB). At the same time, EmiA had no hemolytic activity towards human erythrocytes. In addition, EmiA demonstrated low cytotoxic activity towards the normal HPF line, but possessed cancer selectivity to the K-562 and HCT-116 cell lines. Emericillipsins from the alkalophilic fungus Emericellopsis alkaline are promising treatment alternatives to licensed antifungal drugs for invasive mycosis therapy, especially for multidrug-resistant aspergillosis and cryptococcosis.

We analyzed susceptibility to anidulafungin of yeasts clinical strains of Candida (14 species), Cryptococcus (1 species), Geotrichum (1 species), Rhodotorula (1 species) and Saccharomyces (1 species). We revealed high anidulafungin activity against Candida spp., both common species and rare pathogens of candidiasis. It was found that over 99 % of Candida strains do not have an acquired resistance mechanisms to anidulafungin (microbiological criteria). The anidulafungin is not active against strains of Cryptococcus neoformans and Rhodotorula mucilaginosa.

Установлены и проанализированы уровни чувствительности к 10 противогрибковым препаратам для 12 видов грибов рода Aspergillus, обнаруженных при диагностике пневмомикозов у больных туберкулезом. Определение чувствительности 202 штаммов Aspergillus spp. к антимикотикам проводили методом микроразведений с определением МПК в мкг/мл (система «Sensititre»). Установлено, что возбудители аспергиллеза отличаются по уровням устойчивости к препарату амфотерицин В. Выделены три вида со сниженной чувствительностью к данному препарату: A. terreus (обладает природной устойчивостью к амфотерицину В), а также A. flavus и A. ochraceus (целесообразно определять чувствительность к амфотерицину В до начала лечения). Обнаружена высокая активность вориконазола, итраконазола и позаконазола в отношении грибов Aspergillus spp., за исключением некоторых штаммов A. ustus (возбудитель со сниженной чувствительностью к азольным препаратам, необходимо тестирование до начала лечения), а также нескольких штаммов A. nidulans и A. niger. Предложена модифицированная методика приготовления споровой суспензии грибов Aspergillus spp., повышающая безопасность проведения тестирования чувствительности и достоверность получаемых результатов.

Background: The emergence of antifungal resistance and the limited number of clinically available antifungal drug classes necessitate the development of new agents with improved efficacy and safety. We investigated how linker architecture influences the antifungal activity and lead properties of hybrid triazole-thiazolidine derivatives. Methods: A focused library of triazole-thiazolidine hybrids incorporating alkylamine, amide, cyclic amine, 2-hydroxypropyl, and thiazepane linkers was synthesized and characterized. Antifungal activity was evaluated against reference strains and clinical isolates of Candida spp., Aspergillus fumigatus, dermatophytes, and Cryptococcus neoformans. Structure–activity relationships were analyzed by molecular docking. Selected compounds were further assessed by SCRAPPY profiling, fluorescence microscopy, mammalian-cell cytotoxicity assays, acute oral toxicity studies, and evaluation of microsomal stability and interactions with human CYP450 isoforms. Results: Linker architecture strongly influenced antifungal potency. Amide- and cyclic amine-containing hybrids were generally the most active, whereas simple alkylamide derivatives showed narrower activity profiles. Compound 28 emerged as the most promising lead, exhibiting sub-microgram MIC values against several Candida isolates, particularly C. parapsilosis, and retaining measurable activity against an azole-resistant C. albicans strain. Docking generated putative CYP51-binding models, while SCRAPPY profiling and fluorescence microscopy revealed an azole-like cellular response consistent with perturbation of sterol-associated homeostasis. Compound 28 was tolerated at 300 mg/kg in an acute oral study but showed concentration- and time-dependent cytotoxicity and rapid CYP3A4-mediated microsomal metabolism. Conclusions: Systematic variation of linker architecture identified compound 28 as a promising exploratory antifungal lead. Further optimization should focus on improving metabolic stability and cytotoxicity, together with direct target validation, pharmacokinetic characterization, and in vivo efficacy studies.

The article describes the author’s unifying scheme for identification of micromycetes isolated from culture with rapid differentiation between nine groups of pathogens: ascomycete yeasts; basidiomycete yeasts of the red yeast group; basidiomycete nonpigmented yeasts; ascomycete yeast-like fungi; basidiomycete yeast-like fungi; zygomycosis causative agents; pheogyphomycosis causative agents of the dimorphic black yeast group; pheogyphomycosis causative agents of the mycelial pheoid species; light-coloured mold causative agents of aspergillosis and hyalohyphomycosis. The article also provides the information about species composition and the classification of molds and yeasts, which can persist in the respiratory tract of TB patients. The activity of current antimycotics against different groups of pathogens that cause opportunistic pneumomycoses is characterized.