Optimized LC-MS/MS quantification of tuberculosis drug candidate macozinone (PBTZ169), its dearomatized Meisenheimer Complex and other metabolites, in human plasma and urine.

Tuberculosis, and especially multidrug-resistant tuberculosis (MDR-TB), is a major global health threat which emphasizes the need to develop new agents to improve and shorten treatment of this difficult-to-manage infectious disease. Among the new agents, macozinone (PBTZ169) is one of the most promising candidates, showing extraordinary potency in vitro and in murine models against drug-susceptible and drug-resistant Mycobacterium tuberculosis. A previous analytical method using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) was developed by our group to support phase I clinical trials of PBTZ169.

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.

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.

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.

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 ˂ 27, two-component systems are formed composed of positive polycomplex particles and free polycation.

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.

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.

Brain Natriuretic Peptide (BNP) Affects Growth and Stress Tolerance of Representatives of the Human Microbiome, C01 and DOS7.

Brain natriuretic peptide (BNP) is secreted by the ventricles of the heart during overload to signal heart failure. Slight bilateral skin itching induced by BNP has been associated with response activity of the skin microbiota. In this work, we studied the effect of 25-250,000 pg BNP/mL on the growth, long-term survival, and stress (HO, antibiotics, salinity, heat and pH shock) resistance of human symbiont bacteria: Gram-positive C01 and Gram-negative DOS7.

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 .

Unusual Cytochrome 552 from : Solution NMR Structure and Interaction with Thiocyanate Dehydrogenase.

The search of a putative physiological electron acceptor for thiocyanate dehydrogenase (TcDH) newly discovered in the thiocyanate-oxidizing bacteria revealed an unusually large, single-heme cytochrome (CytC552), which was co-purified with TcDH from the periplasm. Recombinant CytC552, produced in as a mature protein without a signal peptide, has spectral properties similar to the endogenous protein and serves as an in vitro electron acceptor in the TcDH-catalyzed reaction. The CytC552 structure determined by NMR spectroscopy reveals significant differences compared to those of the typical class I bacterial cytochromes : a high solvent accessible surface area for the heme group and so-called "intrinsically disordered" nature of the histidine-rich N- and C-terminal regions.

Microbial Biofilms at Meat-Processing Plant as Possible Places of Bacteria Survival.

Biofilm contamination in food production threatens food quality and safety, and causes bacterial infections. Study of food biofilms (BF) is of great importance. The taxonomic composition and structural organization of five foods BF taken in different workshops of a meat-processing plant (Moscow, RF) were studied.

Insulin Receptor-Related Receptor Regulates the Rate of Early Development in .

The orphan insulin receptor-related receptor (IRR) encoded by gene is the third member of the insulin receptor family, also including the insulin receptor (IR) and the insulin-like growth factor receptor (IGF-1R). IRR is the extracellular alkaline medium sensor. In mice, is expressed only in small populations of cells in specific tissues, which contain extracorporeal liquids of extreme pH.

Application of Special Electron Microscopy Techniques to the Study of DNA - Protein Complexes in E. coli Cells.

Various electron microscopy techniques were applied recently to the study of DNA condensation in dormant bacterial cells. Here, we describe, in detail, the preparation of dormant Escherichia coli cells for electron microscopy studies and electron tomography and energy dispersive spectroscopy (EDS) approaches, which were used to reveal the structures of DNA-protein complexes in dormant Escherichia coli cells.

Constitutive chitosanase from Bacillus thuringiensis B-387 and its potential for preparation of antimicrobial chitooligomers.

The article proves the ability of the entomopathogenic strain B. thuringiensis var. dendrolimus B-387 to high the constitutive production (3-12.

[The analysis of immunoreactivity of individual B-cell epitopes of hepatitis C virus (Flaviviridae: Hepacivirus: Hepatitis С virus) NS4a antigen].

Introduction: Chronic viral hepatitis C (CHC) is a ubiquitous infectious disease, a significant limitation of which WHO attributes to the use of a new highly effective antiviral therapy. Previously, two B-cell epitopes were identified in NS4a antigen of the hepatitis C virus (HCV). It was shown that certain titers of antibodies (ABs) to the extended C-terminal epitope (1687-1718 a.

Structural Bases of Prion Variation in Yeast.

Amyloids are protein aggregates with a specific filamentous structure that are related to a number of human diseases, and also to some important physiological processes in animals and other kingdoms of life. Amyloids in yeast can stably propagate as heritable units, prions. Yeast prions are of interest both on their own and as a model for amyloids and prions in general.

Recent advances in structural studies of 14-3-3 protein complexes.

Being phosphopeptide-binding hubs, 14-3-3 proteins coordinate multiple cellular processes in eukaryotes, including the regulation of apoptosis, cell cycle, ion channels trafficking, transcription, signal transduction, and hormone biosynthesis. Forming constitutive α-helical dimers, 14-3-3 proteins predominantly recognize specifically phosphorylated Ser/Thr sites within their partners; this generally stabilizes phosphotarget conformation and affects its activity, intracellular distribution, dephosphorylation, degradation and interactions with other proteins. Not surprisingly, 14-3-3 complexes are involved in the development of a range of diseases and are considered promising drug targets.