High-Risk Lineages of Hybrid Plasmids Carrying Virulence and Carbapenemase Genes.

Carbapenem-resistant (CRE) are a global health threat due to their high morbidity and mortality rates and limited treatment options. This study examines the plasmid-mediated transmission of virulence and antibiotic resistance determinants in carbapenem-resistant () and () isolated from Russian hospitals. : We performed short- and long-read whole-genome sequencing of 53 clinical isolates (48 and 5 ) attributed to 15 genetic lineages and collected from 21 hospitals across nine Russian cities between 2016 and 2022.

Antioxidant properties of the soluble carotenoprotein AstaP and its feasibility for retinal protection against oxidative stress.

Photodamage to the outer segments of photoreceptor cells and their impaired utilization by retinal pigment epithelium (RPE) cells contribute to the development of age-related macular degeneration (AMD) leading to blindness. Degeneration of photoreceptor cells and RPE cells is triggered by reactive oxygen species (ROS) produced by photochemical reactions involving bisretinoids, by-products of the visual cycle, which accumulate in photoreceptor discs and lipofuscin granules of RPE. Carotenoids, natural antioxidants with high potential efficacy against a wide range of ROS, may protect against the cytotoxic properties of lipofuscin.

Accumulation of Li Ions Triggers Changes in , , , and Transcription in the LiCl-Treated Human Umbilical Vein Endothelial Cells (HUVEC).

Changes in intracellular concentrations of Na and K are shown to alter gene expression. Another monovalent cation, Li, is well known as a medicine for treatment of psychiatric disorders, but mechanism of its action is obscure. Thus, it is important to evaluate the effect of Li on gene expression in endothelial cells.

Minimum inhibitory concentrations of aztreonam-avibactam, ceftazidime-avibactam and meropenem in clinical isolates of Klebsiella pneumoniae harboring carbapenemase genes.

This study was aimed at understanding the distributions of the MICs (minimum inhibitory concentrations) of aztreonam-avibactam, ceftazidime-avibactam and meropenem with respect to Klebsiella pneumoniae isolates producing different types of carbapenemases and their combinations. K. pneumoniae isolates were collected between 2019 and 2022 from 37 hospitals.

G-Quadruplexes as Sensors of Intracellular Na+/K Ratio: Potential Role in Regulation of Transcription and Translation.

Data on the structure of G-quadruplexes, noncanonical nucleic acid forms, supporting an idea of their potential participation in regulation of gene expression in response to the change in intracellular Na+/K+ ratio are considered in the review. Structural variety of G-quadruplexes, role of monovalent cations in formation of this structure, and thermodynamic stability of G-quadruplexes are described. Data on the methods of their identification in the cells and biological functions of these structures are presented.

[Metabolic Stress of Red Blood Cells Induces Hemoglobin Glutathionylation].

Metabolic stress caused by a lack of glucose significantly affects the state of red blood cells, where glycolysis is the main pathway for the production of ATP. Hypoglycemia can be both physiological (occurring during fasting and heavy physical exertion) and pathological (accompanying a number of diseases, such as diabetes mellitus). In this study, we have characterized the state of isolated erythrocytes under metabolic stress caused by the absence of glucose.

[Identification of Melittin-Like Proteins with a Molecular Weight of 67 κDa that Interact with Na^(+)/K^(+)-ATPase].

Melittin, a peptide from bee venom, was found to be able to interact with many proteins, including calmodulin target proteins and ion-transporting P-type ATPases. It is assumed that melittin mimics a protein module involved in protein-protein interactions within cells. Previously, a Na^(+)/K^(+)-ATPase containing the α1 isoform of the catalytic subunit was found to co-precipitate with a protein with a molecular weight of about 70 κDa that interacts with antibodies against melittin by cross immunoprecipitation.

Synthesis of methylphosphorylated oligomannosides structurally related to lipopolysaccharide O-antigens of serotype O3 and their application for detection of specific antibodies in rabbit and human sera.

Methylphosphorylated mono-, di- and trimannosides structurally related to the lipopolysaccharide (LPS) O-antigens of of serotype O3 were synthesized and conjugated with a biotin tag. The stereo- and regioselective assembly of target carbohydrate chains was conducted using uniform monosaccharide synthetic blocks. After that, a methylphosphate group was introduced by coupling with a methyl-H-phosphonate reagent followed by oxidation and deprotection to give the target oligosaccharides.

Testing the mutant selection window hypothesis with meropenem: In vitro model study with OXA-48-producing Klebsiella pneumoniae.

OXA-48 carbapenemases are frequently expressed by Klebsiella pneumoniae clinical isolates; they decrease the effectiveness of carbapenem therapy, particularly with meropenem. Among these isolates, meropenem-susceptible carbapenemase-producers may show decreased meropenem effectiveness. However, the probability of the emergence of resistance in susceptible carbapenemase-producing isolates and its dependence on specific K.

Phenotypic and genomic characteristics of oxacillin-susceptible mecA-positive Staphylococcus aureus, rapid selection of high-level resistance to beta-lactams.

The aim of this study is to describe the phenotypic and genetic properties of oxacillin-susceptible methicillin-resistant Staphylococcus aureus (OS-MRSA) isolates and their beta-lactam resistant derivatives obtained after selection with oxacillin. A collection of hospital- (HA-) and community-acquired (CA-) MRSA was screened for oxacillin susceptibility. Antibiotic susceptibility testing, population analysis profile (PAP), mecA expression analysis, and whole genome sequencing (WGS) were performed for 60 mecA-positive OS-MRSA isolates.

Adaptive Laboratory Evolution of Resistance to Vancomycin and Daptomycin: Mutation Patterns and Cross-Resistance.

Vancomycin and daptomycin are first-line drugs for the treatment of complicated methicillin-resistant (MRSA) infections, including bacteremia. However, their effectiveness is limited not only by their resistance to each antibiotic but also by their associated resistance to both drugs. It is unknown whether novel lipoglycopeptides can overcome this associated resistance.

Sodium Ions as Regulators of Transcription in Mammalian Cells.

The maintenance of an uneven distribution of Na+ and K+ ions between the cytoplasm and extracellular medium is the basis for the functioning of any animal cell. Changes in the intracellular ratio of these cations occur in response to numerous stimuli and are important for the cell activity regulation. Numerous experimental data have shown that gene transcription in mammalian cells can be regulated by changes in the intracellular [Na+]/[K+] ratio.

Country data on AMR in Russia in the context of community-acquired respiratory tract infections: links between antibiotic susceptibility, local and international antibiotic prescribing guidelines, access to medicine and clinical outcome.

Background: Antimicrobial reistance (AMR) is one of the biggest threats to global public health. Selection of resistant bacteria is driven by inappropriate use of antibiotics, amongst other factors. COVID-19 may have exacerbated AMR due to unnecessary antibiotic prescribing.

Increased Extracellular Sodium Concentration as a Factor Regulating Gene Expression in Endothelium.

Hyperosmotic stimulation of endothelial cells often leads to its dysfunction accompanied, among other things, by proinflammatory response. The mechanisms of this phenomenon are not fully understood. It may arise due to increase in the plasma Na+ concentration, due to increase in the extracellular osmolarity, increase in the intracellular Na+/K+ ratio, and/or change in the cell stiffness.

Susceptibility to Carbapenem/Relebactam Combinations: Influence of Inoculum Density and Carbapenem-to-Inhibitor Concentration Ratio.

The inoculum effect (IE) is a well-known phenomenon with beta-lactams. At the same time, the IE has not been extensively studied with carbapenem/carbapenemase inhibitor combinations. The antibiotic-to-inhibitor concentration ratio used in susceptibility testing can influence the in vitro activity of the combination.

Antimicrobial properties of a new polymeric material based on poly(2-hydroxyethyl methacrylate).

Background And Aim: Оne of the promising areas is the development of synthetic wound dressings with programmed release of active substances that can affect various elements in the pathogenesis of the wound process. The aim was to study the antimicrobial properties of a new polymeric material based on poly(2-hydroxyethyl methacrylate).

Methods: 2-hydroxyethyl methacrylate, dimethacrylate triethylene glycol as crosslinking agent, polymerization initiator of azobisizobutyronitrile along with a porogen and one of the antimicrobial agents, including decamethoxin, chlorhexidine bigluconate, silver nitrate, octenidine, furacilin, metronidazole, dioxidine, and gentamicin were used to synthesize a new material with antimicrobial activity.

[Tumnin mineral spring. History of development].

The article dwells upon the history of the discovery of the Tumnin mineral spring, the establishment and development of the Far Eastern health resort «Goryachy Klyuch,» located in the basin of Chope creek, a tributary of the largest river in the eastern macroslope of Sikhote Alin, Tumnin river, located 25 km from the Strait of Tartary. A historical sketch since the first mentioning of the Tumnin mineral spring from 1903 to the present day, as well as the results of hydrogeological expeditions to determine the chemical composition and α-activity of Tumnin mineral water at different periods, are presented. A contribution of a geological expedition that established a large deep-lying tectonic structure permeable to upwelling thermal water flows is described.

Na /K imbalance contributes to gene expression in endothelial cells exposed to elevated NaCl.

High-salt consumption contributes to the development of hypertension and is considered an independent risk factor for vascular remodelling, cardiac hypertrophy and stroke incidence. Alterations in NO production, inflammation and endothelial cell stiffening are considered now as plausible mediators of cardiovascular dysfunction. We studied early responses of endothelial cells (HUVEC) caused by a moderate increase in extracellular sodium concentration.

Global Expansion of Linezolid-Resistant Coagulase-Negative Staphylococci.

Coagulase-negative staphylococci (CoNS) for a long time were considered avirulent constituents of the human and warm-blooded animal microbiota. However, at present, , , and are recognized as opportunistic pathogens. Although linezolid is not registered for the treatment of CoNS infections, it is widely used off-label, promoting emergence of resistance.

Emergence of Hybrid Resistance and Virulence Plasmids Harboring New Delhi Metallo-β-Lactamase in in Russia.

The emergence of carbapenem-resistant hypervirulent (CR-hvKp) is a new threat to healthcare. In this study, we analyzed nine CR-hvKp isolates of different sequence-types (ST) recovered from patients with nosocomial infections in two hospitals in Saint Petersburg. Whole-genome sequencing showed that eight of them harbored large mosaic plasmids carrying resistance to carbapenems and hypervirulence simultaneously, and four different types of hybrid plasmids were identified.

In Vitro Selection of High-Level Beta-Lactam Resistance in Methicillin-Susceptible .

Selective pressure of beta-lactams is thought to be responsible for mutation selection in methicillin-susceptible (MSSA). We used next-generation sequencing to compare the genomes of beta-lactamase-positive (SA0707) and -negative (SA0937) MSSA isolates with their derivatives obtained after selection with oxacillin, ceftaroline, or meropenem. Selection with oxacillin and ceftaroline caused a rapid and significant (6-8 times) increase in the minimum inhibitory concentration (MICs) of oxacillin, penicillin, amoxicillin/clavulanate, and ceftaroline against the derivatives of both isolates, associated with growth impairment.

CD150 and CD180 are negative regulators of IL-10 expression and secretion in chronic lymphocytic leukemia B cells.

Chronic lymphocytic leukemia (CLL) is a strikingly heterogeneous disease both at the molecular level and clinical disease course. The malignant B cells obtain key proliferation and survival signals within lymph nodes or bone marrow. Moreover, CLL B cells and tumor microenvironment dynamically co-evolve organizing inflammatory and immunosuppressive microenvironment by direct contact with surrounding cells and secretion of cytokines, growth factors, or extracellular vesicles.