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We have performed a characterization of cultivated haloalkalitolerant fungi from the sediments of Big Tambukan Lake in order to assess their biodiversity and antimicrobial activity. This saline, slightly alkaline lake is known as a source of therapeutic sulfide mud used in sanatoria of the Caucasian Mineral Waters, Russia. Though data on bacteria and algae observed in this lake are available in the literature, data on fungi adapted to the conditions of the lake are lacking. The diversity of haloalkalitolerant fungi was low and represented by ascomycetes of the genera Acremonium, Alternaria, Aspergillus, Chordomyces, Emericellopsis, Fusarium, Gibellulopsis, Myriodontium, Penicillium, and Pseudeurotium. Most of the fungi were characterized by moderate alkaline resistance, and they tolerated NaCl concentrations up to 10% w/v. The analysis of the antimicrobial activity of fungi showed that 87.5% of all strains were active against Bacillus subtilis, and 39.6% were also determined to be effective against Escherichia coli. The majority of the strains were also active against Aspergillus niger and Candida albicans, about 66.7% and 62.5%, respectively. These studies indicate, for the first time, the presence of polyextremotolerant fungi in the sediments of Big Tambukan Lake, which probably reflects their involvement in the formation of therapeutic muds. [ABSTRACT FROM AUTHOR]

Peptaibols (Paib) are a class of biologically active peptides isolated from fungi and molds, which have attracted the attention of medicinal chemists due to their widely ranging pharmacological properties, including their antimicrobial activity. In the present study, we investigated the effects of various pH levels and cultivation conditions on peptaibol complex emericellipsins A-E (EmiA-E), produced by the alkaliphilic fungus Emericellopsis alkalina. Paib production has been studied in flasks and bioreactors for different pH values ranging from 7 to 11. The study of morphological features based on light and scanning electron microscopy has revealed differences between fungi grown at different pH values and cultivation conditions. Emericellipsins have been purified, sequenced, and identified by mass spectrometry. We have found that an alkaline pH of 10 could promote emericellipsins' biosynthesis most effectively during stationary fermentation on the 14th day of cultivation. [ABSTRACT FROM AUTHOR]

Sustained interest in the use of renewable resources for the production of medical materials has stimulated research on bacterial cellulose (BC) and nanocomposites based on it. New Ag-containing nanocomposites were obtained by modifying various forms of BC with Ag nanoparticles prepared by metal–vapor synthesis (MVS). Bacterial cellulose was obtained in the form of films (BCF) and spherical BC beads (SBCB) by the Gluconacetobacter hansenii GH-1/2008 strain under static and dynamic conditions. The Ag nanoparticles synthesized in 2-propanol were incorporated into the polymer matrix using metal-containing organosol. MVS is based on the interaction of extremely reactive atomic metals formed by evaporation in vacuum at a pressure of 10−2 Pa with organic substances during their co-condensation on the cooled walls of a reaction vessel. The composition, structure, and electronic state of the metal in the materials were characterized by transmission and scanning electron microscopy (TEM, SEM), powder X-ray diffraction (XRD), small-angle X-ray scattering (SAXS) and X-ray photoelectron spectroscopy (XPS). Since antimicrobial activity is largely determined by the surface composition, much attention was paid to studying its properties by XPS, a surface-sensitive method, at a sampling depth about 10 nm. C 1s and O 1s spectra were analyzed self-consistently. XPS C 1s spectra of the original and Ag-containing celluloses showed an increase in the intensity of the C-C/C-H groups in the latter, which are associated with carbon shell surrounding metal in Ag nanoparticles (Ag NPs). The size effect observed in Ag 3d spectra evidenced on a large proportion of silver nanoparticles with a size of less than 3 nm in the near-surface region. Ag NPs in the BC films and spherical beads were mainly in the zerovalent state. BC-based nanocomposites with Ag nanoparticles exhibited antimicrobial activity against Bacillus subtilis, Staphylococcus aureus, Escherichia coli bacteria and Candida albicans and Aspergillus niger fungi. It was found that AgNPs/SBCB nanocomposites are more active than Ag NPs/BCF samples, especially against Candida albicans and Aspergillus niger fungi. These results increase the possibility of their medical application. [ABSTRACT FROM AUTHOR]

New hybrid materials based on Ag nanoparticles stabilized by a polyaminopropylalkoxysiloxane hyperbranched polymer matrix were prepared. The Ag nanoparticles were synthesized in 2-propanol by metal vapor synthesis (MVS) and incorporated into the polymer matrix using metal-containing organosol. MVS is based on the interaction of extremely reactive atomic metals formed by evaporation in high vacuum (10−4–10−5 Torr) with organic substances during their co-condensation on the cooled walls of a reaction vessel. Polyaminopropylsiloxanes with hyperbranched molecular architectures were obtained in the process of heterofunctional polycondensation of the corresponding AB2-type monosodiumoxoorganodialkoxysilanes derived from the commercially available aminopropyltrialkoxysilanes. The nanocomposites were characterized using transmission (TEM) and scanning (SEM) electron microscopy, X-ray photoelectron spectroscopy (XPS), powder X-ray diffraction (PXRD) and Fourier-transform infrared spectroscopy (FTIR). TEM images show that Ag nanoparticles stabilized in the polymer matrix have an average size of 5.3 nm. In the Ag-containing composite, the metal nanoparticles have a "core-shell" structure, in which the "core" and "shell" represent the M0 and Mδ+ states, respectively. Nanocomposites based on silver nanoparticles stabilized with amine-containing polyorganosiloxane polymers showed antimicrobial activity against Bacillus subtilis and Escherichia coli. [ABSTRACT FROM AUTHOR]

An amorphous carbon film with embedded detonation nanodiamond (DND) particles (a-C:ND) was produced by magnetron sputtering of nanodiamond powder. An Ag film was deposited on the carbon structure by radiofrequency magnetron sputtering. The silver film was irradiated with a 150 eV Ar+ to form plasmonic-active nanoparticles (NP) on the surface of the a-C:ND. The structure of the obtained a-C:ND and a-C:ND/Ag structures were studied by scanning and transmission electron microscopy, electron energy-loss spectroscopy, UV–Visible absorption spectroscopy, Raman spectroscopy, and fluorescence lifetime imaging at two-photon excitation. The analysis revealed 76% of sp3-carbon and a good dispersion of diamond nanoparticles in the a-C. Surface-enhanced Raman scattering (SERS) was applied to investigate the a-C:ND/Ag structure, allowing for the observation of SERS from the sp2-carbon species and the absence of significant a-C:ND damage after Ar+ irradiation of the Ag overlayer. A plasmonic-metal-enhanced luminescence was observed at one- and two-photon excitations, revealing a two- to five-fold intensity increase. The activity of the used DNDs was tested using the agar diffusion method and observed against the bacteria of Bacillus subtilis, Staphylococcus aureus, and Escherichia coli and the fungi of Aspergillus niger, Aspergillus fumigatus, and the yeast of Candida albicans, showing DND activity against all the test strains of fungi. [ABSTRACT FROM AUTHOR]

Methods for creating various 3D morphologies of composites based on chitosan and copper nanoparticles stabilized by it in carbonic acid solutions formed under high pressure of saturating CO2 were developed. This work includes a comprehensive analysis of the regularities of copper nanoparticles stabilization and reduction with chitosan, studied by IR and UV-vis spectroscopies, XPS, TEM and rheology. Chitosan can partially reduce Cu2+ ions in aqueous solutions to small-sized, spherical copper nanoparticles with a low degree of polydispersity; the process is accompanied by the formation of an elastic polymer hydrogel. The resulting composites demonstrate antimicrobial activity against both fungi and bacteria. Exposing the hydrogels to the mixture of He or H2 gases and CO2 fluid under high pressure makes it possible to increase the porosity of hydrogels significantly, as well as decrease their pore size. Composite capsules show sufficient resistance to various conditions and reusable catalytic activity in the reduction of nitrobenzene to aniline reaction. The relative simplicity of the proposed method and at the same time its profound advantages (such as environmental friendliness, extra purity) indicate an interesting role of this study for various applications of materials based on chitosan and metals. [ABSTRACT FROM AUTHOR]

A number of bacteria that colonize the human body produce toxins and effectors that cause changes in the eukaryotic cell cycle—cyclomodulins and low-molecular-weight compounds such as butyrate, lactic acid, and secondary bile acids. Cyclomodulins and metabolites are necessary for bacteria as adaptation factors—which are influenced by direct selection—to the ecological niches of the host. In the process of establishing two-way communication with the macroorganism, these compounds cause limited damage to the host, despite their ability to disrupt key processes in eukaryotic cells, which can lead to pathological changes. Possible negative consequences of cyclomodulin and metabolite actions include their potential role in carcinogenesis, in particular, with the ability to cause DNA damage, increase genome instability, and interfere with cancer-associated regulatory pathways. In this review, we aim to examine cyclomodulins and bacterial metabolites as important factors in bacterial survival and interaction with the host organism to show their heterogeneous effect on oncogenesis depending on the surrounding microenvironment, pathological conditions, and host genetic background. [ABSTRACT FROM AUTHOR]

Gausemycin A is the first member of the novel lipoglycopeptides family produced by Streptomyces roseoflavus INA-Ac-5812. Gausemycin A has a pronounced bactericidal activity against methicillin-resistant Staphylococcus aureus. However, the ability of S. aureus to be resistant to gausemycin A has not been investigated yet. Using serial passaging, we have obtained the resistant variant S. aureus 5812R, which is 80 times more resistant compared to the parent strain. Susceptibility testing of S. aureus 5812R revealed the acquisition of cross-resistance to daptomycin, cefazolin, tetracycline, and gentamicin, while the resistance to vancomycin, nisin, and ramoplanin was absent. Whole genome sequencing revealed single nucleotide polymorphism (SNP) and deletions in S. aureus 5812R, among which are genes encoding efflux pump (sepA), the two-component Kdp system (kdpE), and the component of isoprenoid biosynthesis pathway (hepT). Phenotypically, S. aureus 5812R resembles a small-colony variant, as it is slow-growing, forms small colonies, and is deficient in pigments. Profiling of fatty acids (FA) composition constituting the cytoplasmic membrane of S. aureus 5812R revealed the prevalence of anteiso-branched FA, while straight FA was slightly less present. The evidence also showed that the gausemycin A-resistant strain has increased expression of the cls2 gene of the cardiolipin synthase. The performed checkerboard assay pointed out that the combination of gausemycin A and ciprofloxacin showed a synergistic effect against S. aureus 5812R. [ABSTRACT FROM AUTHOR]

New functional medical materials with antibacterial activity based on biocompatible bacterial cellulose (BC) and Ag nanoparticles (Ag NPs) were obtained. Bacterial cellulose films were prepared by stationary liquid-phase cultivation of the Gluconacetobacter hansenii strain GH-1/2008 in Hestrin–Schramm medium with glucose as a carbon source. To functionalize the surface and immobilize Ag NPs deposited by magnetron sputtering, BC films were treated with low-pressure oxygen–nitrogen plasma. The composition and structure of the nanomaterials were studied using transmission (TEM) and scanning (SEM) electron microscopy and X-ray photoelectron spectroscopy (XPS). Using electron microscopy, it was shown that on the surface of the fibrils that make up the network of bacterial cellulose, Ag particles are stabilized in the form of aggregates 5–35 nm in size. The XPS C 1s spectra show that after the deposition of Ag NPs, the relative intensities of the C-OH and O-C-O bonds are significantly reduced. This may indicate the destruction of BC oxypyran rings and the oxidation of alcohol groups. In the Ag 3d5/2 spectrum, two states at 368.4 and 369.7 eV with relative intensities of 0.86 and 0.14 are distinguished, which are assigned to Ag0 state and Ag acetate, respectively. Nanocomposites based on plasma-treated BC and Ag nanoparticles deposited by magnetron sputtering (BCP-Ag) exhibited antimicrobial activity against Aspergillus niger, S. aureus and Bacillus subtilis. [ABSTRACT FROM AUTHOR]

The adaptations that alkaliphilic microorganisms have developed due to their extreme habitats promote the production of active natural compounds with the potential to control microorganisms, causing infections associated with healthcare. The primary purpose of this study was to isolate and identify a hydrophobin, Sa-HFB1, from an alkaliphilic fungus, Sodiomyces alkalinus. A potential antifungal effect against pathogenic and opportunistic fungi strains was determined. The MICs of Sa-HFB1 against opportunistic and clinical fungi ranged from 1 to 8 µg/mL and confirmed its higher activity against both non- and clinical isolates. The highest level of antifungal activity (MIC 1 µg/mL) was demonstrated for the clinical isolate Cryptococcus neoformans 297 m. The hydrophobin Sa-HFB1 may be partly responsible for the reported antifungal activity of S. alkalinus, and may serve as a potential source of lead compounds, meaning that it can be developed as an antifungal drug candidate. [ABSTRACT FROM AUTHOR]

Polymer microgels, including those based on interpenetrating networks (IPNs), are currently vastly studied, and their practical applications are a matter of thriving research. In this work, we show the perspective for the use of polyelectrolyte IPN microgels either as scavengers or carriers of antiseptic substances. Here, we report that poly-N-isopropylacrylamide/polyacrylic acid IPN microgels can efficiently absorb the common bactericidal and virucidal compound benzalkonium chloride. The particles can form a stable aqueous colloidal suspension or be used as building blocks for soft free-standing films. Both materials showed antiseptic efficacy on the examples of Bacillus subtilis and S. aureus, which was approximately equal to the commercial antibiotic. Such polymer biocides can be used as liquid disinfectants, stable surface coatings, or parts of biomedical devices and can enhance the versatility of the possible practical applications of polymer microgels. [ABSTRACT FROM AUTHOR]

Features of the biochemical adaptations of alkaliphilic fungi to exist in extreme environments could promote the production of active antibiotic compounds with the potential to control microorganisms, causing infections associated with health care. Thirty-eight alkaliphilic and alkalitolerant Emericellopsis strains (E. alkalina, E. cf. maritima, E. cf. terricola, Emericellopsis sp.) isolated from different saline soda soils and belonging to marine, terrestrial, and soda soil ecological clades were investigated for emericellipsin A (EmiA) biosynthesis, an antifungal peptaibol previously described for Emericellopsis alkalina. The analysis of the Emericellopsis sp. strains belonging to marine and terrestrial clades from chloride soils revealed another novel form with a mass of 1032.7 Da, defined by MALDI-TOF Ms/Ms spectrometers, as the EmiA lacked a hydroxyl (dEmiA). EmiA displayed strong inhibitory effects on cell proliferation and viability of HCT 116 cells in a dose- and time-dependent manners and induced apoptosis. [ABSTRACT FROM AUTHOR]

The creation of biocompatible composite hydrogels from renewable biopolymers with stabilized functional platinum nanoparticles seems to be an important scientific task. The formation of such hydrogels in a unique medium of carbonic acid under high pressure CO2 is promising due to its sterilizing ability under pressure, biocompatibility after decompression and environmental friendliness. In the present work, stable chitosan hydrogels with platinum nanoparticles were obtained in such solutions. The hydrogel nature of the composites was confirmed by rotational rheology. The physicochemical characteristics were studied using Fourier transform infrared, X‐ray photoelectron, ultraviolet–visible spectroscopies, transmission electron, scanning electron and atomic force microscopies. It was found that nanoparticles of oxidized Pt of approximately 4.5 nm in size are stabilized by chitosan in the composite. The resulting chitosan/Pt hydrogels were also tested for antimicrobial activity and shown strong activity against Gram‐positive bacteria (B. subtilis and B. coagulans) and slight activity against E. coli. [ABSTRACT FROM AUTHOR]

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 multidrugresistant aspergillosis and cryptococcosis. [ABSTRACT FROM AUTHOR]

In this work, we report the isolation and detailed functional characterization for the new non-ribosomally synthesized antibiotic 5812-A/C, which was derived from metabolites of Streptomyces roseoflavus INA-Ac-5812. According to its chemical structure, the studied 5812-A/C preliminary is composed of a cyclic peptide part covalently bounded with an arabinose residue. N-terminal amino acid sequencing of the native peptide has identified its partial structure of Leu-Asp-Gly-Ser-Gly and consisting of a Tyr residue that is supposed to have a two-component peptide nature for the molecule studied. However, the structural analysis of the antibiotic complex derived from S. roseoflavus INA-Ac-5812 is still ongoing. The mechanism of action of 5812-A/C was assessed in comparison with its most related analog, the lipopeptide antibiotic daptomycin, given the presence in both antimicrobials of an L-kynurenine amino acid residue. The inhibitory activity of 5812-A/C against Gram-positive bacteria including methicillin-resistant strain of Staphylococcus aureus was similar to daptomycin. The mechanism of action of 5812-A/C was associated with the disruption of membrane integrity, which differs in comparison with daptomycin and is most similar to the antimicrobial membrane-disturbing peptides. However, 5812-A/C demonstrated a calcium-dependent mode of action. In addition, unlike daptomycin, 5812-A/C was able to penetrate mature biofilms and inhibit the metabolic activity of embedded S. aureus cells. At the same time, 5812-A/C has no hemolytic activity toward erythrocyte, but possessed weak cytotoxic activity represented by heterochromatin condensation in human buccal epithelium cells. The biological properties of the peptide 5812-A/C suggest its classification as a calcium-dependent antibiotic effective against a wide spectrum of Gram-positive pathogenic bacteria. [ABSTRACT FROM AUTHOR]

High-cationic biologically active peptides of the thionins family were isolated from black cumin (Nigella sativa L.) seeds. According to their physicochemical characteristics, they were classified as representatives of the class I thionin subfamily. Novel peptides were called "Nigellothionins", so-called because of their source plant. Thionins are described as components of plant innate immunity to environmental stress factors. Nine nigellothionins were identified in the plant in different amounts. Complete amino acid sequences were determined for three of them, and a high degree of similarity was detected. Three nigellothionins were examined for antifungal properties against collection strains. The dominant peptide, NsW2, was also examined for activity against clinical isolates of fungi. Cytotoxic activity was determined for NsW2. Nigellothionins activity against all collection strains and clinical isolates varied from absence to a value comparable to amphotericin B, which can be explained by the presence of amino acid substitutions in their sequences. Cytotoxic activity in vitro for NsW2 was detected at sub-micromolar concentrations. This has allowed us to propose an alteration of the molecular mechanism of action at different concentrations. The results obtained suggest that nigellothionins are natural compounds that can be used as antimycotic and anti-proliferative agents. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Composite fibers and films based on cellulose and betulin were spun for the first time from solutions in N-methylmorpholine-N-oxide using the dry–wet jet method. The rheological properties of the composite solutions did not reveal any fundamental difference from those of the cellulose solutions. Introduction of betulin into the cellulose matrix (up to 10%) led to a decrease in the mechanical properties of the obtained fibers. The structure of the composite fibers was analyzed using SEM and X-ray diffraction methods. It was shown that the introduction of an additive into the cellulose matrix led to a decrease in the structural ordering of the cellulose. Comparative studies of the antibacterial activity of the composite films on Escherichia coli (E. coli) were carried out. The antifungal activity of the composite films was estimated using the strain of the O-97 Trichoderma viride Pers ex Fr (Gause Institute of New Antibiotics, Moscow, Russia). [ABSTRACT FROM AUTHOR]

Abstract Two new natural compounds, astolides A,B, were isolated from Streptomyces hygroscopicus collected from the alkaline soil obtained from Saratov region, Russia. The structures were elucidated by interpretation of UV spectroscopic, MS, 1D and 2D NMR data. The relative configurations were determined by analysis of NOESY/ROESY spectra and coupling constants. The isolated compounds were evaluated for their inhibitory activity against bacteria, fungi and yeasts and showed pronounced antifungal activity. Both compounds are noticeably cytotoxic, being active against doxorubicin-resistant human leukemia cell line. Graphical abstract Two new natural products astolides A,B from Streptomyces hygroscopicus show pronounced antifungal and cytotoxic activity. Image 1 [ABSTRACT FROM AUTHOR]