Identification of genetic determinants of bedaquiline resistance in in Ural region, Russia.

Unlabelled: Collecting data on rare () clinical isolates with resistance to the new anti-tuberculosis drug bedaquiline is an important task for improving antimicrobial susceptibility testing methods. Nanopore whole genome sequencing, the proportion method on Middlebrook 7H11 medium, and BACTEC MGIT 960 assays were used to analyze genotypic and phenotypic resistance to bedaquiline. We found four mutations: I66M, А63Р, А36Т, and S53P in five isolates with different levels of phenotypic bedaquiline resistance.

Drug-Tolerant Adopt Different Survival Strategies in Alveolar Macrophages of Patients with Pulmonary Tuberculosis.

The rapid spread of drug-resistant () strains and the phenomenon of phenotypic tolerance to drugs present challenges toward achieving the goal of tuberculosis (TB) elimination worldwide. By using the ex vivo cultures of alveolar macrophages obtained from lung tissues of TB patients after intensive antimicrobial chemotherapy before surgery, different subpopulations of multidrug-tolerant with a spectrum of phenotypic and growth features were identified in the same TB lesions. Our results are indicative of not only passive mechanisms generating nonheritable resistance of to antibiotics, which are associated mainly with a lack of growth, but also some active mechanisms of persistence, such as cell wall and metabolic pathway remodeling.

Molecular characteristics of Mycobacterium tuberculosis drug-resistant isolates from HIV- and HIV+ tuberculosis patients in Russia.

Background: High burden of drug-resistant (DR) tuberculosis (TB) is a significant threat to national TB control programs all over the world and in the Russian Federation. Different Mycobacterium tuberculosis (MTB) genotypes are hypothesized to have specific characteristics affecting TB control programs. For example, Beijing strains are supposed to have higher mutation rates compared to strains of other genotypes and subsequently higher capability to develop drug-resistance.

Load in Host Cells and the Antibacterial Activity of Alveolar Macrophages Are Linked and Differentially Regulated in Various Lung Lesions of Patients with Pulmonary Tuberculosis.

Tuberculosis (TB) is a disease caused by () infection with the formation of a broad range of abnormal lung lesions within a single patient. Although host-pathogen interactions determine disease outcome, they are poorly understood within individual lesions at different stages of maturation. We compared load in a tuberculoma wall and the lung tissue distant from tuberculomas in TB patients.

Analysis of Mycobacterium tuberculosis Uptake by Alveolar Macrophages after Ex vivo Expansion Indicates Processing Host Cells with Pathogen Actually from Lung Tissue of Patients with Pulmonary Tuberculosis.

Background: Previously, the ex vivo cultures of alveolar macrophages were developed from the surgical samples of the lungs in patients with pulmonary tuberculosis (TB) to establish the unique features of Mycobacterium tuberculosis (Mtb) lifestyle in host cells, but the question has remained whether Mtb-infected cells are isolated from the human lungs or they may be the result of Mtb phagocytosis in ex vivo culture. The study was aimed to investigate Mtb uptake by TB patients' cells after ex vivo expansion.

Methods: Alveolar macrophages were infected with the Mtb clinical isolates in ex vivo culture, and the acid-fast Mtb loads in the cells were analyzed.

Molecular characteristics of Mycobacterium tuberculosis in the "closed" Russian town with limited population migration.

The aim of this study was to perform a molecular characterization of Mycobacterium tuberculosis strains circulating in one of the "closed" Russian cities under conditions of the limited population migration and high HIV coinfection rate. We analyzed 109 M. tuberculosis isolates recovered from TB patients in the Novouralsk municipality in the Ural area of Russia; 38.

Mycobacterium tuberculosis with different virulence reside within intact phagosomes and inhibit phagolysosomal biogenesis in alveolar macrophages of patients with pulmonary tuberculosis.

Tuberculosis (TB) is a dangerous airborne disease caused by Mycobacterium tuberculosis (Mtb) and characterized by a tight interplay between pathogen and host cells, mainly alveolar macrophages. Studies of the mechanisms of Mtb survival within human cells during TB disease are extremely important for the development of new strategies and drugs for TB treatment. We have used the ex vivo cultures of alveolar macrophages and histological sections obtained from the resected lungs of patients with pulmonary TB to establish the unique features of Mtb lifestyle in host cells.

Mycobacterium tuberculosis cording in alveolar macrophages of patients with pulmonary tuberculosis is likely associated with increased mycobacterial virulence.

Mycobacterium tuberculosis (Mtb) is an infectious agent that causes tuberculosis (TB) in humans. A study of the volume of Mtb population and the detection of Mtb virulence in the lungs of patients with pulmonary TB are of great importance for understanding the infectious process and the outcome of the disease. We analyzed the functional state of Mtb and their number in alveolar macrophages obtained from the resected lungs of patients with TB in ex vivo culture and determined that the number of Mtb, referred mainly to the Beijing genotype family (A0 and B0/W148 clusters), were significantly different in cells between different patients.

The recombinant fusion protein CFP10-ESAT6-dIFN has protective effect against tuberculosis in guinea pigs.

Development of effective vaccine candidates against tuberculosis is currently the most important challenge in the prevention of this disease since the BCG vaccine fails to guarantee a lifelong protection, while any other approved vaccine with better efficiency is still absent. The protective effect of the recombinant fusion protein ESAT6-CFP10-dIFN produced in a prokaryotic expression system (Escherichia coli) has been assessed in a guinea pig model of acute tuberculosis. The tested antigen comprises the Mycobacterium tuberculosis (Mtb) proteins ESAT6 and CFP10 as well as modified human γ-interferon (dIFN) for boosting the immune response.

Ex vivo expansion of alveolar macrophages with Mycobacterium tuberculosis from the resected lungs of patients with pulmonary tuberculosis.

Tuberculosis (TB), with the Mycobacterium tuberculosis (Mtb) as the causative agent, remains to be a serious world health problem. Traditional methods used for the study of Mtb in the lungs of TB patients do not provide information about the number and functional status of Mtb, especially if Mtb are located in alveolar macrophages. We have developed a technique to produce ex vivo cultures of cells from different parts of lung tissues surgically removed from patients with pulmonary TB and compared data on the number of cells with Mtb inferred by the proposed technique to the results of bacteriological and histological analyses used for examination of the resected lungs.

The recombinant fusion protein CFP10-ESAT6-dIFN has protective effect against tuberculosis in guinea pigs.

Development of effective vaccine candidates against tuberculosis (TB) is currently the most important challenge in the prevention of this disease since the BCG vaccine fails to guarantee a lifelong protection, while any other approved vaccine with better efficiency is still absent. The protective effect of the recombinant fusion protein CFP10-ESAT6-dIFN produced in a prokaryotic expression system (Escherichia coli) has been assessed in a guinea pig model of acute TB. The tested antigen comprises the Mycobacterium tuberculosis (Mtb) proteins ESAT6 and CFP10 as well as modified human γ-interferon (dIFN) for boosting the immune response.

Distribution and diversity of Nosema bombi (Microsporidia: Nosematidae) in the natural populations of bumblebees (Bombus spp.) from West Siberia.

Nosema bombi is an obligate intracellular parasite of bumblebees (Hymenoptera, Bombus spp.), which has significant negative effect on individual bumblebees, colony fitness, and development. Recently, several new genetic variants of N.

[Experience of application of ultrasound dissection-aspiration in surgical treatment of extracerebral intracranial tumors].

The results of surgical treatment of 33 patients, suffering intracranial extracerebral tumours, were analyzed. Magnet-resonance tomography of the brain, selective angiography with contrasting of external and internal carotid and vertebral arteries were used for neurovisualization, in several patients-bilaterally. In 19 (57.