Screening, identification, and antibiotic activity of secondary metabolites of Penicillium sp. LPB2019K3-2 isolated from endemic amphipods of Lake Baikal

This study aimed to assess the influence of nutrient media content on the production of antibiotics and the ability of water fungi isolated from lake Baikal to synthesize novel natural products. Interest in this topic stems from the high demand for new drugs, and studies are carried out via the screening of new natural products with biological activity produced by unstudied or extremophilic microorganisms. For this study, a strain of Penicillium sp. was isolated from endemic Baikal phytophagous amphipod species. Here, we identified natural products using the following classical assays: biotechnological cultivation, MALDI identification of the strain, natural product extraction, antimicrobial activity determination, and modern methods such as HPLC-MS for the dereplication and description of natural products. It was found that many detected metabolites were not included in the most extensive database. Most of the identified metabolites were characterized by their biological activity and demonstrated antibiotic activity against model Gram-positive and Gram-negative bacteria. The isolated strain of water fungus produced penicolinate B, meleagrin A, austinoneol A, andrastin A, and other natural products. Additionally, we show that the synthesis of low-molecular-weight natural products depends on the composition of the microbiological nutrient media used for cultivation. Thus, although the golden age of antibiotics ended many years ago and microscopic fungi are well studied producers of known antibiotics, the water fungi of the Lake Baikal ecosystem possess great potential in the search for new natural products for the development of new drugs. These natural products can become new pharmaceuticals and can be used in therapy to treat new diseases such as SARS, MERS, H5N1, etc

FIRST REPORT ON TRUFFLE-INHABITING FUNGI AND METAGENOMIC COMMUNITIES OF TUBER AESTIVUM COLLECTED IN RUSSIA

Truffles are one of the least studied groups of fungi in terms of their biological and biotechnological aspects. This study aimed to isolate truffle-inhabiting fungi and assess the metagenomic communities of the most common Russian summer truffle, Tuber aestivum. This study is the first to characterize the biodiversity of prokaryotic and eukaryotic organisms living in the truffle T. aestivum using molecular analysis and sequencing. Plant pathogens involved in a symbiotic relationship with truffles were identified by sequencing the hypervariable fragments of the 16S rRNA and 18S rRNA genes. In addition, some strains of fungal symbionts and likely pathogens were isolated and recognized for the first time from the truffles. This study also compared and characterized the general diversity and distribution of microbial taxa of T. aestivum collected in Russia and Europe. The results revealed that the Russian and European truffle study materials demonstrated high similarity. In addition to the truffles, representatives of bacteria, fungi, and protists were found in the fruiting bodies. Many of these prokaryotic and eukaryotic species inhabiting truffles might influence them, help them form mycorrhizae with trees, and regulate biological processes. Thus, truffles are interesting and promising sources for modern biotechnological and agricultural studies

Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis

Allergic rhinitis is the most common clinical presentation of allergy, affecting 400 million people worldwide, with increasing incidence in westernized countries1,2. To elucidate the genetic architecture and understand the underlying disease mechanisms, we carried out a meta-analysis of allergic rhinitis in 59,762 cases and 152,358 controls of European ancestry and identified a total of 41 risk loci for allergic rhinitis, including 20 loci not previously associated with allergic rhinitis, which were confirmed in a replication phase of 60,720 cases and 618,527 controls. Functional annotation implicated genes involved in various immune pathways, and fine mapping of the HLA region suggested amino acid variants important for antigen binding. We further performed genome-wide association study (GWAS) analyses of allergic sensitization against inhalant allergens and nonallergic rhinitis, which suggested shared genetic mechanisms across rhinitis-related traits. Future studies of the identified loci and genes might identify novel targets for treatment and prevention of allergic rhinitis

The Use of Baikal Psychrophilic Actinobacteria for Synthesis of Biologically Active Natural Products from Sawdust Waste

One of the relevant areas in microbiology and biotechnology is the study of microorganisms that induce the destruction of different materials, buildings, and machines and lead to negative effects. At the same time, the positive ecological effects of degradation can be explained by the detoxication of industrial and agricultural wastes, chemical substances, petroleum products, xenobiotics, pesticides, and other chemical pollutants. Many of these industrial wastes include hard-to-degrade components, such as lignocellulose or plastics. The biosynthesis of natural products based on the transformation of lignocellulosic wastes is of particular interest. One of the world’s unique ecosystems is presented by Lake Baikal. This ecosystem is characterized by the highest level of biodiversity, low temperatures, and a high purity of the water. Here, we studied the ability of several psychrophilic representatives of Baikal Actinobacteria to grow on sawdust wastes and transform them into bioactive natural products. Different strains of both widely spread genus of Actinobacteria and rare genera of Actinobacteria were tested. We used the LC-MS methods to show that Actinobacteria living in sawmill wastes can produce both known and novel natural products with antibiotic activity. We demonstrated that the type of sawmill wastes and their concentration influence the Actinobacteria biosynthetic potential. We have shown for the first time that the use of Baikal psychrophilic microorganisms as a factory for biodegradation is applicable for the transformation of lignocellulosic wastes. Thus, the development of techniques for screening novel natural products leads to an elaboration on the active ingredients for novel drugs

The Use of Baikal Psychrophilic Actinobacteria for Synthesis of Biologically Active Natural Products from Sawdust Waste

One of the relevant areas in microbiology and biotechnology is the study of microorganisms that induce the destruction of different materials, buildings, and machines and lead to negative effects. At the same time, the positive ecological effects of degradation can be explained by the detoxication of industrial and agricultural wastes, chemical substances, petroleum products, xenobiotics, pesticides, and other chemical pollutants. Many of these industrial wastes include hard-to-degrade components, such as lignocellulose or plastics. The biosynthesis of natural products based on the transformation of lignocellulosic wastes is of particular interest. One of the world’s unique ecosystems is presented by Lake Baikal. This ecosystem is characterized by the highest level of biodiversity, low temperatures, and a high purity of the water. Here, we studied the ability of several psychrophilic representatives of Baikal Actinobacteria to grow on sawdust wastes and transform them into bioactive natural products. Different strains of both widely spread genus of Actinobacteria and rare genera of Actinobacteria were tested. We used the LC-MS methods to show that Actinobacteria living in sawmill wastes can produce both known and novel natural products with antibiotic activity. We demonstrated that the type of sawmill wastes and their concentration influence the Actinobacteria biosynthetic potential. We have shown for the first time that the use of Baikal psychrophilic microorganisms as a factory for biodegradation is applicable for the transformation of lignocellulosic wastes. Thus, the development of techniques for screening novel natural products leads to an elaboration on the active ingredients for novel drugs

Europe Centrale Mitteleuropa

Depuis leur institutionnalisation en France à la fin du XIXe siècle, les études germaniques ont cherché à s’inscrire dans un cadre interdisciplinaire. Moyen d’accès essentiel à la connaissance du monde germanique, l’histoire littéraire stricto sensu n’a jamais constitué leur base exclusive, pas plus que la linguistique. La Revue germanique internationale renoue avec cette conception d’une histoire culturelle de l’aire germanophone, communicable au public de toutes les « spécialités ». Elle sera un lieu de rencontre des historiens, des philosophes, des comparatistes, des sociologues et des auteurs des différentes disciplines que l’intérêt porté aux pays de langue allemande réunit avec les germanistes. La connaissance de l’Allemagne réunifiée et la compréhension de la place qui lui revient dans une Europe centrale en pleine recomposition rendent plus que jamais nécessaire une information solide sur les spécificités intellectuelles, sur la diversité et sur les traditions qui font de notre voisin le plus familier un étranger toujours mal connu. La « germanistique » allemande a souvent eu pour finalité l’affirmation d’une identité nationale. Les études françaises sur les pays de langue allemande n’ont pas à reprendre cette orientation, mais plutôt à profiter de leur situation extérieure pour envisager les problèmes de la territorialité culturelle allemande, les symptômes de cirse, les imbrications avec d’autres cultures. Les différenciations entre les identités nationales et régionales qui composent le grand ensemble germanique, les transferts culturels franco-allemands, le judaïsme, la constitution d’une conscience européenne, les contacts entre la « Mitteleuropa » et l’Europe orientale fournissent autant de points d’appui à cette démarche. La revue sera internationale : non seulement franco-germanique, mais aussi ouverte aux chercheurs d’autres pays, pour peu qu’ils partagent un même intérêt pour des questions d’histoire culturelle ouvrant les frontières des territoires de langue allemande

C. elegans lifespan extension by osmotic stress requires FUdR, base excision repair, FOXO, and sirtuins

Moderate stress can increase lifespan by hormesis, a beneficial low-level induction of stress response pathways. 5'-fluorodeoxyuridine (FUdR) is commonly used to sterilize Caenorhabditis elegans in aging experiments. However, FUdR alters lifespan in some genotypes and induces resistance to thermal and proteotoxic stress. We report that hypertonic stress in combination with FUdR treatment or inhibition of the FUdR target thymidylate synthase, TYMS-1, extends C. elegans lifespan by up to 30%. By contrast, in the absence of FUdR, hypertonic stress decreases lifespan. Adaptation to hypertonic stress requires diminished Notch signaling and loss of Notch co-ligands leads to lifespan extension only in combination with FUdR. Either FUdR treatment or TYMS-1 loss induced resistance to acute hypertonic stress, anoxia, and thermal stress. FUdR treatment increased expression of DAF-16 FOXO and the osmolyte biosynthesis enzyme GPDH-1. FUdR-induced hypertonic stress resistance was partially dependent on sirtuins and base excision repair (BER) pathways, while FUdR-induced lifespan extension under hypertonic stress conditions requires DAF-16, BER, and sirtuin function. Combined, these results demonstrate that FUdR, through inhibition of TYMS-1, activates stress response pathways in somatic tissues to confer hormetic resistance to acute and chronic stress. C. elegans lifespan studies using FUdR may need re-interpretation in light of this work.Peer reviewe

Perfluorocarbon Nanoemulsions with Fluorous Chlorin-Type Photosensitizers for Antitumor Photodynamic Therapy in Hypoxia

The efficacy of photodynamic therapy (PDT) strictly depends on the availability of molecular oxygen to trigger the light-induced generation of reactive species. Fluorocarbons have an increased ability to dissolve oxygen and are attractive tools for gas delivery. We synthesized three fluorous derivatives of chlorin with peripheral polyfluoroalkyl substituents. These compounds were used as precursors for preparing nanoemulsions with perfluorodecalin as an oxygen depot. Therefore, our formulations contained hydrophobic photosensitizers capable of absorbing monochromatic light in the long wavelength region and the oxygen carrier. These modifications did not alter the photosensitizing characteristics of chlorin such as the generation of singlet oxygen, the major cytocidal species in PDT. Emulsions readily entered HCT116 colon carcinoma cells and accumulated largely in mitochondria. Illumination of cells loaded with emulsions rapidly caused peroxidation of lipids and the loss of the plasma membrane integrity (photonecrosis). Most importantly, in PDT settings, emulsions potently sensitized cells cultured under prolonged (8 weeks) hypoxia as well as cells after oxygen depletion with sodium sulfite (acute hypoxia). The photodamaging potency of emulsions in hypoxia was significantly more pronounced compared to emulsion-free counterparts. Considering a negligible dark cytotoxicity, our materials emerge as efficient and biocompatible instruments for PDT-assisted eradication of hypoxic cells

Effect of low-dose gaseous ozone on pathogenic bacteria

<p>Abstract</p> <p>Background</p> <p>Treatment of chronically infected wounds is a challenge, and bacterial environmental contamination is a growing issue in infection control. Ozone may have a role in these situations. The objective of this study was to determine whether a low dose of gaseous ozone/oxygen mixture eliminates pathogenic bacteria cultivated in Petri dishes.</p> <p>Methods</p> <p>A pilot study with 6 bacterial strains was made using different concentrations of ozone in an ozone-oxygen mixture to determine a minimally effective dose that completely eliminated bacterial growth. The small and apparently bactericidal gaseous dose of 20 μg/mL ozone/oxygen (1:99) mixture, applied for 5min under atmospheric pressure was selected. In the 2^nd phase, eight bacterial strains with well characterized resistance patterns were evaluated <it>in vitro</it> using agar-blood in adapted Petri dishes (10⁵ bacteria/dish). The cultures were divided into 3 groups: 1- ozone-oxygen gaseous mixture containing 20 μg of O₃/mL for 5 min; 2- 100% oxygen for 5 min; 3- baseline: no gas was used.</p> <p>Results</p> <p>The selected ozone dose was applied to the following eight strains: <it>Escherichia coli</it>, oxacillin-resistant <it>Staphylococcus aureus</it>, oxacillin-susceptible <it>Staphylococcus aureus</it>, vancomycin-resistant <it>Enterococcus faecalis</it>, extended-spectrum beta-lactamase-producing <it>Klebsiella pneumoniae</it>, carbapenem-resistant <it>Acinetobacter baumannii</it>, <it>Acinetobacter baumannii</it> susceptible only to carbapenems, and <it>Pseudomonas aeruginosa</it> susceptible to imipenem and meropenem. All isolates were completely inhibited by the ozone-oxygen mixture while growth occurred in the other 2 groups.</p> <p>Conclusion</p> <p>A single topical application by nebulization of a low ozone dose completely inhibited the growth of all potentially pathogenic bacterial strains with known resistance to antimicrobial agents.</p