Semisynthetic Amides of Polyene Antibiotic Natamycin.

Natamycin is a macrolide polyene antibiotic, characterized by a potent broad spectrum antifungal activity and low toxicity. However, it is not used for the treatment of systemic mycoses due to its low bioavailability and low solubility in aqueous solutions. In order to create new semisynthetic antifungal agents for treatment of mycoses, a series of water-soluble amides of natamycin were synthesized.

Biodegradable Interpolycomplexes for Anti-Erosion Stabilization of Soil and Sand.

A linear anionic polysaccharide, sodium alginate, electrostatically interacts with a cationic polysaccharide, quaternized hydroxyethyl cellulose ethoxylate, in aqueous solution, thus giving an interpolyelectrolyte complex. Aqueous solutions of the initial polysaccharides and polycomplexes with an excess of the cationic or anionic polymers were used for the stabilization of soil and sand against water erosion. Physicochemical, mechanical and biological properties of the polymers and coatings were characterized by gravimetric analysis, viscosimetry, mechanical strength assessment, cell viability, and cell-mediated degradation with the following main conclusions.

The Role of the 145 Residue in Photochemical Properties of the Biphotochromic Protein mSAASoti: Brightness versus Photoconversion.

Photoswitchable fluorescent proteins (FPs) have become indispensable tools for studying life sciences. mSAASoti FP, a biphotochromic FP, is an important representative of this protein family. We created a series of mSAASoti mutants in order to obtain fast photoswitchable variants with high brightness.

VapC toxin switches M. smegmatis cells into dormancy through 23S rRNA cleavage.

Mycobacterium tuberculosis is an extremely successful pathogen known for its ability to cause latent infection. The latter is connected with the bacterium resting state development and is considered to be based on the activity of toxin-antitoxin (TA) systems at least in part. Here we studied the physiological and proteomic consequences of VapC toxin overexpression together with the features of the protein synthesis apparatus and compared them with the characteristics of dormant mycobacterial cells in an M.

Antituberculosis Macozinone Extended-Release Tablets To Enhance Bioavailability: a Pilot Pharmacokinetic Study in Beagle Dogs.

Macozinone (MCZ; PBTZ169) is a first-in-class antituberculosis clinical-stage benzothiazinone-based drug candidate. Although its efficacy and safety have been strongly proven in several preclinical and clinical studies, the physicochemical and pharmacokinetic properties specific to MCZ required further optimization. Accordingly, this study aimed to evaluate the pharmacokinetics of MCZ administered as extended-release (ER) tablets F2 and F6 compared to immediate-release (IR) dispersible tablets for oral suspension.

Effects of Molecular Crowding and Betaine on HSPB5 Interactions, with Target Proteins Differing in the Quaternary Structure and Aggregation Mechanism.

The aggregation of intracellular proteins may be enhanced under stress. The expression of heat-shock proteins (HSPs) and the accumulation of osmolytes are among the cellular protective mechanisms in these conditions. In addition, one should remember that the cell environment is highly crowded.

Spermidine and 1,3-Diaminopropane Have Opposite Effects on the Final Stage of Cephalosporin C Biosynthesis in High-Yielding Strain.

The addition of exogenous polyamines increases the production of antibiotic cephalosporin C (CPC) in high-yielding (HY) strain during fermentation on a complex medium. However, the molecular basis of this phenomenon is still unknown. In the current study, we developed a special synthetic medium on which we revealed the opposite effect of polyamines.

[Genetic Engineering in Mycobacteria].

Genetic tools for targeted modification of the mycobacterial genome contribute to the understanding of the physiology and virulence mechanisms of mycobacteria. Human and animal pathogens, such as the Mycobacterium tuberculosis complex, which causes tuberculosis, and M. leprae, which causes leprosy, are of particular importance.

[CRISPR Interference in Regulation of Bacterial Gene Expression].

The review is devoted to the use of the CRISPR/Cas system for obtaining knockdowns of target bacterial genes by CRISPR-mediated interference (CRISPRi). CRISPRi is based on the preservation of the ability of the inactivated dCas nuclease in complex with guide RNA to bind a target, which leads to reversible repression of the selected genes. The review describes the principle of operation of CRISPR/Cas and CRIS-PRi/dCas and provides examples of various approaches to the use of CRISPRi with the most popular inactivated nucleases dCas9 and dCas12a.

Single substitution in α-helix of active center enhanced thermostability of Aspergillus awamori exo-inulinase.

Exo-inulinases are applied in inulin hydrolysis and production of feed additives and need to be stable at temperatures of 60-95 °C. Aspergillus awamori exo-inulinase Inu1 is considerably thermostable, with a T of 73.2 °C.

Interaction of Antibiotics and Humic Substances: Environmental Consequences and Remediation Prospects.

The occurrence and distribution of antibiotics in the environment has received increasing attention due to their potential adverse effects on human health and ecosystems. Humic substances (HS) influence the mobility, reactivity, and bioavailability of antibiotics in the environment significantly due to their interaction. As a result, HS can affect the dissemination of antibiotic-resistance genes, which is one of the main problems arising from contamination with antibiotics.

New Effective Method of Lactococcus Genome Editing Using Guide RNA-Directed Transposition.

is an important industrial microorganism and a widely used model object for research in the field of lactic acid bacteria (LAB) biology. The development of new and related LAB strains with improved properties, including phage-resistant strains for dairy fermentation, LAB-based vaccines or strains with altered genotypes for research purposes, are hindered by the lack of genome-editing tools that allow for the easy and straightforward incorporation of a significant amount of the novel genetic material, such as large genes or operons, into the chromosomes of these bacteria. We recently employed a suggested system based on the CRISPR-Cas-associated transposon for the editing of the genome.

Box-Behnken assisted development and validation of high-performance liquid chromatography method for the simultaneous determination of doxorubicin and vorinostat in polymeric nanoparticles.

While histone deacetylase inhibitors, such as vorinostat, demonstrate a significant effect against hematological cancers, their application for solid tumor treatment is limited. However, there is strong evidence that combinatorial administration of vorinostat and genotoxic agents (e.g.

Biocidal Coatings from Complexes of Carboxylated Latex Particles and a Linear Cationic Polymer.

A linear polycation, poly(diallyldimethylammonium chloride), electrostatically interacts with anionic latex particles from a carboxylated butadiene-styrene copolymer in aqueous solution thus forming an interpolyelectrolyte complex. A mutual neutralization of oppositely charged latex and polycation groups occurs at = latex/polycation = 50 ratio. At = 27, an ultimate polycation adsorption is reached, resulting in the formation of positive polycomplex particles, while at Ë‚ 27, two-component systems are formed composed of positive polycomplex particles and free polycation.

Electrophoresis-Assisted Multilayer Assembly of Nanoparticles for Sensitive Lateral Flow Immunoassay.

Lateral flow immunoassay (LFIA) is a rapid, simple, and inexpensive point-of-need method. A major limitation of LFIA is a high limit of detection (LOD), which impacts its diagnostic sensitivity. To overcome this limitation, we introduce a signal-enhancement procedure that is performed after completing LFIA and involves controllably moving biotin- and streptavidin-functionalized gold nanoparticles by electrophoresis.

Dependence of the content of starch and reducing sugars on the level of expression of the genes of β-amylases StBAM1 and StBAM9 and the amylase inhibitor StAI during long-term low-temperature storage of potato tubers.

Solanum tuberosum L. is the most important non-grain starch crop with a potential yield of 38-48 t/ha and a starch content of 13.2-18.

Influence of the Active Site Flexibility on the Efficiency of Substrate Activation in the Active Sites of Bi-Zinc Metallo-β-Lactamases.

The influence of the active site flexibility on the efficiency of catalytic reaction is studied by taking two members of metallo-β-lactamases, L1 and NDM-1, with the same substrate, imipenem. Active sites of these proteins are covered by L10 loops, and differences in their amino acid compositions affect their rigidity. A more flexible loop in the NDM-1 brings additional flexibility to the active site in the ES complex.

Effect of Mineral Carriers on Biofilm Formation and Nitrogen Removal Activity by an Indigenous Anammox Community from Cold Groundwater Ecosystem Alone and Bioaugmented with Biomass from a "Warm" Anammox Reactor.

The complex pollution of aquifers by reduced and oxidized nitrogen compounds is currently considered one of the urgent environmental problems that require non-standard solutions. This work was a laboratory-scale trial to show the feasibility of using various mineral carriers to create a permeable in situ barrier in cold (10 °C) aquifers with extremely high nitrogen pollution and inhabited by the Scalindua-dominated indigenous anammox community. It has been established that for the removal of ammonium and nitrite in situ due to the predominant contribution of the anammox process, quartz, kaolin clays of the Kantatsky and Kamalinsky deposits, bentonite clay of the Berezovsky deposit, and zeolite of the Kholinsky deposit can be used as components of the permeable barrier.

TRIM28 regulates transcriptional activity of methyl-DNA binding protein Kaiso by SUMOylation.

Kaiso is a methyl DNA binding transcriptional factor involved in cell cycle control, WNT signaling, colon inflammation, and cancer progression. Recently, it was shown that SUMOylation dynamically modulates the transcriptional activity of Kaiso. However, factors involved in SUMOylation of Kaiso are unknown.

Enhancement of activity and thermostability of Aspergillus niger ATCC 10864 phytase A through rational design.

Aspergillus niger ATCC 10864 phytase A was produced in Penicillium verruculosum. The enzyme was found to have two pH optima of 2.5 and 5.

Epinephrine extensively changes the biofilm matrix composition in C01 isolated from human skin.

The importance of the impact of human hormones on commensal microbiota and microbial biofilms is established in lots of studies. In the present investigation, we continued and extended the research of epinephrine effects on the skin commensal C01 and its biofilms, and also the matrix changes during the biofilm growth. Epinephrine in concentration 4.

Didecyldimethylammonium Chloride- and Polyhexamethylene Guanidine-Resistant Bacteria Isolated from Fecal Sludge and Their Potential Use in Biological Products for the Detoxification of Biocide-Contaminated Wastewater Prior to Conventional Biological Treatment.

Toxic shock caused by the discharge of biocide-contaminated fecal sludge (FS) from chemical toilets to conventional wastewater treatment plants (WWTP) can be a major problem in activated sludge operation. It is necessary to develop new environmental approaches to mitigate the toxicity of biocides in order to avoid degrading the performance of WWTP. "Latrina", a chemical toilet additive containing didecyldimethylammonium chloride and polyhexamethylene guanidine, is widely used in environmentally safe toilet complexes (ESTC) on Russian railway trains to deodorize FS and control microbial activity.

PDSTP Is the First Drug in Class to Treat Coronavirus Infection.

The results of a comprehensive study are presented on the development and creation of an original small PDSTP molecule, able to prevent the SARS-CoV-2 coronavirus infection from binding to the host cell. The PDSTP molecule was designed to electrostatically interact with heparan sulfate proteoglycans on the cell surface, and coronaviruses, particularly SARS-CoV-2, use this mechanism as the first stage of interaction with the cell. By blocking this process, it is possible to stop the life cycle of the virus, thus leading to its death.

The GEM-GECO Calcium Indicator Is Useable in Yeast, but Aggravates Effects of Increased Cytosolic Calcium Levels.

Ca is a ubiquitous second messenger, which allows eukaryotic cells to respond to external stimuli. The use of genetically encoded Ca indicators allows real-time monitoring of cytosolic Ca levels to study such responses. Here we explored the possibility of using the ratiometric Ca indicator GEM-GECO for monitoring cytosolic Ca concentration ([Ca]) in the yeast .