Salmonella, the agent causing salmonellosis, is one of the most common food pathogens in the world. Bacteriophages are now considered as the most effective and environmentally friendly method to control pathogens in various food products. We evaluated the efficacy of Salmonella phage BF1354 in decontamination of chicken fillet samples artificially contaminated with antibiotic-resistant Salmonella. Sterile chicken fillet samples (5 × 5 cm2) were artificially contaminated with Salmonella Enteritidis and then treated with bacteriophage at a concentration of 109 PFU/ml. The samples were stored at 4°C for 10 days. The number of Salmonella on days 1, 6, and 10 of the experiment decreased by 2.1, 2, and 0.8 log(CFU/g), respectively, in comparison with the control. The results demonstrate the efficacy of bacteriophage BF1354 in reducing the number of Salmonella cells in chicken fillets at refrigerated storage temperatures.

The toxicity and safety of a veterinary anti-salmonella disinfectant based on three highly virulent bacteriophage strains (titers 1010 PFU/ml) were studied. Acute, chronic, and inhalation toxicity, as well as local irritancy of the disinfectant were evaluated on outbred white mice CD1 (n=65), Soviet chinchilla rabbits (n=20), and rats (n=20). No toxic effects of the disinfectant was observed after its intraperitoneal or intragastric administration to mice and intragastric administration to rats; in rabbits, application on the skin and eyes produced no local irritation effect. Inhalation of 10% of the disinfectant did not cause any pathologies in mice. Thus, the tests confirmed the high level of safety of the disinfectant based on a mixture of bacteriophages for use as an additional specific disinfection agent against Salmonella in veterinary and livestock facilities.

Two bacteriophages specifically active against to pathogenic strains of the Salmonella genus were isolated. The morphology of phage colonies (size, transparency, and shape of the plaque edge, and halo) and the spectrum of their lytic activity and interaction with microbial cells (adsorption rate, duration of the latency, and reproductive efficiency) were examined. Using genome-wide sequencing, we determined the taxonomic position of bacteriophages and verified the absence of unwanted genes encoding toxins, adhesins, and invasins, as well as pathogenicity islands responsible for antibiotic resistance. In addition, phage stability under different physical conditions and their productivity were studied.

The modern concepts of lectins and glycoconjugates binding to them, the features and patterns of their interaction, the protective role and potential in the human body are summarized. The analysis of terms, approaches to classifications of lectins is carried out. The features of natural and synthetic glycoconjugates, recognized and bound by lectins, in symbiotic relationships, in innate immunity at the reception level are emphasized. The levels of specificity of lectins are considered. There is a need to expand research on the glycoconjugate specificity of lectins and their systems, to assess the communication potential of glycoconjugates in relation to any protein combinations and systems as lectins. The participation of lectin and glycoconjugate systems in signal transmission and communication is noted. Lectins manifest themselves as basic for superstructure glycoconjugate effectors in soluble and solid cell phases in cascade directed assemblies forming the interactome network. Lectins and glycoconjugates, as inextricably co-functioning, are promising in biology, medicine and biotechnologies.

Due to the coronavirus pandemic in Russia, a significant increase in the emergence of strains of microorganisms with multiple drug resistance was noted.Objective: improvement of the effectiveness of prophylactic and therapeutic measures aimed at prevention of hospital pathogens circulation in the intensive care unit by using bacteriophages active against multidrug-resistant strains of Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, and Acinetobacter baumannii.Materials and methods. The study was conducted on the basis of the Intensive Care Unit No. 2 of L.A. Vorohobov City Clinical Hospital No. 67 of Moscow Healthcare Department. Personalized selection of bacteriophages was carried out on the basis of G.N. Gabrichevsky Moscow Research Institute of Epidemiology and Microbiology. The study included two groups of patients, a total of 20 people, who were on prolonged mechanical ventilation in the intensive care unit.Results. No toxic and allergic reactions were detected from the patients in all cases of bacteriophages application. Pathological changes of blood biochemical parameters were not observed in connection with the use of bacteriophages. Complete eradication of pathogens occurred in 60 % of cases.Conclusion. The effectiveness of treatment of various nosological forms of HAIs caused by MDR strains of hospital pathogens increased by 30%, and the effectiveness of the starting antibiotic therapy regimen was 70% and more as a result of the use of personalized phage therapy.

Keeping rhesus monkeys as laboratory animals requires timely prevention and treatment of infections, including diseases of bacterial etiology. Based on our own studies of the microflora of healthy and sick monkeys, as well as analysis of published reports, we identified clinically significant representatives of pathogenic and opportunistic bacteria: E. coli, Staphylococcus aureus, Klebsiella spp., Proteus spp. The isolates of these bacterial species and genera circulating in monkeys kept in the enclosure were isolated, four virulent bacteriophage strains with a wide spectrum of lytic activity against these isolates were selected and newly isolated. The composition based on virulent bacteriophage strains was tested on monkeys with assessment of its safety and its dynamics of detection of phage-specific DNA.

The scope of the study is to study the biological properties of dietary supplements line: LactoBalance multiprobiotic, Neobiotic Lactobalance and Neobiotic Lactobalance Baby/Lactobalance Baby, isolation and generic identification of probiotic microorganisms from samples, confirmation of their growth properties and study of their antibiotic resistance. Materials and methods. The study confirmed that the number of probiotic microorganisms in the Lactobalance product line corresponds to those declared by the manufacturer. From biologically active food additives, probiotic microorganisms were isolated, identified and classified according to GOST R 56139-2014, MU 2.3.2.2789-10 [6, 7] and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF). Isolation and cultivation of bifidobacteria strains and thermophilic streptococcus were carried out on a nutrient medium for the cultivation and isolation of bifidobacteria (FBSI SSC PMB, Obolensk, Russia), lactobacilli strains – on a nutrient medium MRS (HiMedia Laboratories Pvt. Limited, India). The growth properties of isolated probiotic microorganisms were studied by passaging them on nutrient media and their resistance to the most clinically significant antibiotics (Amoxicillin + clavulanic acid, Cefixime, Ciprofloxacin, Azithromycin, Clarithromycin, Levofloxacin, Oxacillin) and to the antiprotozoal and antimicrobial substance Metronidazole was determined using 2 methods: disco-diffusion method (DDM) and minimum inhibitory concentration (MIC) using strips. The studies used antibiotic discs and MIC strips manufactured by HiMedia Laboratories Pvt. Limited (India), Liofilchem srl. (Italy). Results. From the studied samples of dietary supplements, probiotic bacteria were isolated and identified (11 strains of bifidobacteria, 7 strains of lactobacilli and 1 strain of thermophilic streptococcus, which corresponds to those declared by the manufacturers). The number of living probiotic microorganisms was determined and their growth properties were confirmed. When studying the bacteria included in Lactobalance, almost all isolated strains and, in general, consortia of bacteria had resistance or low natural sensitivity to cefixime and ciprofloxacin, oxacillin. All lactobacilli were naturally resistant to metronidazole. Among bifidobacteria, the B. longum strain was resistant to metronidazole. All bacteria were highly sensitive to levofloxacin, amoxicillin with clavulanic acid, azithromycin and clarithromycin. As part of Neobiotic Lactobalance and Neobiotic Lactobalance Baby/Lactobalance Baby, 84% of the isolated bacteria, as well as the consortium of bacteria, were resistant or had low sensitivity to ciprofloxacin, cefixime, metronidazole and oxacillin. B. bifidum was resistant to azithromycin and clarithromycin. All isolated bacteria showed sensitivity to amoxicillin with clavulanic acid and levofloxacin, but the consortium of bifidobacteria showed high sensitivity only to amoxicillin with clavulanic acid. The decrease in sensitivity to other antibiotics is associated with the synergy of the properties of individual strains. Conclusion. Based on the results of in vitro studies, it can be concluded that the probiotic bacteria included in the Lactobalance dietary supplement line correspond to the declared species and their quantity and retain their growth properties. When taking all dietary supplements in the Lactobalance line while taking antibiotic therapy with cefixime, ciprofloxacin and oxacillin, as well as taking metronidazole, there is a possibility of colonization of the intestinal mucosa with probiotic strains included in their composition. When taking Neobiotic Lactobalance and Neobiotic Lactobalance Baby/Lactobalance Baby, there is a possibility of colonization of the intestinal mucosa with probiotic strains while taking cefixime, metronidazole, ciprofloxacin, oxacillin, azithromycin and clarithromycin. Key words: probiotics, bifidobacteria, lactobacilli, thermophilic streptococcus, natural antibiotic resistance, minimum inhibitory concentration of antimicrobial drugs

Airborne infections constitute an extensive group of human diseases. The first barrier to the penetration of infectious agents is the oropharyngeal mucosa, where the autonomic immune system plays a special role. Therefore, maintaining the active function of mucosal immunity and its correction in situ, in the focus of inflammation, is an important way to stop respiratory infections. The coronavirus pandemic has spurred the search for effective means of preventing and treating viral diseases. Various nasal formulations have been proposed with barrier, virucidal, anti-inflammatory and antibacterial properties. An important place belongs to antibodies directed against a specific pathogen, for which it is proposed to use monoclonal antibodies, antibodies isolated from eggs of immunized chickens, nano-antibodies of representatives of the Camelid family, or colostrum antibodies of vaccinated cows. In our opinion, it is more attractive to use antibodies isolated from human blood plasma, which have a wide spectrum of activity, therefore, in the case of mixed infection or difficult diagnosis, they can have a preventive or therapeutic effect against many pathogens. Nasal drops or spray containing human immunoglobulin can be an effective treatment for many bacterial and viral infections, including COVID-19. Key words: аirborne infections, COVID-19, prevention, nasal drugs, antibodies, human immunoglobulin

Objective. In simulation modeling, to study the airborne transmission of respiratory viruses to medical personnel during dental treatment of patients. Materials and methods. During the complex treatment of chronic periodontitis with the use of a bacteriophage preparation, a simulation of the airborne respiratory infection viruses was performed. The spread of the staphylococcal phage was evaluated in 50 air samples and 190 flushes from the doctor, his personal protective equipment, tools and environmental objects by a modified Grazia method on the target bacteria of non-pathogenic Staphylococcus xylosus. The identification of the bacteriophage was carried out in PCR. Results. In the complex treatment of periodontitis in patients using bacteriophages, it was detected in 84.00% [95% CI 63.92–95.46] dental office air samples with maximum frequency in the patient's treatment area, the doctor's and assistant's areas (100.00% [95% CI 47.82–134.48]). The bacteriophage equally contaminated the inner surfaces of the medical mask and the nasal cavity of the doctor (p = 0.62). The maximum amount of phage was isolated from dental equipment: air-water syringe ((35.30 ± 10.55)·107 PFU/ml) and an ultrasonic scaler ((23.02 ± 7.72)·107 PFU/ml). Conclusion. The use of aerosol-generating procedures in the treatment of dental diseases is accompanied by intensive contamination by viruses of the air of the dental office, environmental objects and personal protective equipment, which determine the high risks of infection of medical care workers. Key words: aerosol generating technologies, bacteriophage, airborne transmission, medical care workers, patients, dentistry

Bovine colostrum (ВС) has a high biological value, which allows it to be used for the development of new functional products. The aim of the study was to assess the possibility of using BC for the prevention and treatment of infectious and non-infectious diseases. Material and methods. The search for scientific information on the study of the component composition, immunobiological properties and the use of BC in clinical practice was carried out using the databases of the RSCI, CyberLeninka, ScienceDirect, PubMed. Results. The macro- and micronutrient composition of BC is presented, its changes over time from the moment of calving are described. A comparative analysis of the content of various components in milk and colostrum is presented. A detailed list of antimicrobial factors that increase nonspecific resistance and provide immunocorrective, antimicrobial and anti-inflammatory effects is submitted. The possibility of using BC in clinical practice as a part of complex therapy in the treatment of various infectious diseases, including severe acute respiratory syndrome caused by the new coronavirus infe ction SARS-CoV-2, as well as in cardiovascular diseases, allergies, autoimmune and oncological diseases, has been demonstrated. Conclusion. According to the literature, BC has a high safety profile and is applicable to all age groups of the population. Given the wide range of biological activity of BC components, a promising area of scientific research is the development of the products for therapeutic and prophylactic purposes, including dietary supplements, based on its ingredients, which have the desired properties for correcting the immune status, preventing non-communicable and infectious diseases, as well as for prevention of occupational diseases among persons working in harmful working conditions.

IgM and IgG antibodies to the SARS-CoV-2 virus are detected in subjects who have recovered from COVID-19; IgM antibodies persist in a 1/3 of infected subjects up to 12 months from the moment of the disease, while IgG antibodies are present in the vast majority of cases (97%; medium and high levels antibodies were registered in 85% of cases). By the 12th month, 40% of those who recovered still have a very high level of IgG antibodies to the S-protein (>500 BAU/ml). In the feces, urine, and blood serum of patients with long-term persistent IgM antibodies, no coronavirus antigens were detected. After vaccination with the Gam-COVID-Vac vaccine, IgG antibodies to the S-protein are detected in 100% of cases and remain at a high level for 4 months, by the 5-6th month, the level of antibodies decreases. During revaccination, the level of IgG antibodies to S-protein reaches high values earlier than during primary vaccination, and remains high for 4 months (observation period). The blood sera of recovered and vaccinated patients have a high virus-neutralizing activity (at least 1:80), while its level is somewhat higher in recovered patients.

Introduction. Infectious otitis externa and middle ear can cause hearing loss, which significantly reduces the quality of life of patients. The main causative agents of acute bacterial otitis media are Pseudomonas aeruginosa and Staphylococcus aureus. This article is devoted to the development and study of a novel dosage form for treatment of infectious diseases of the external ear containing bacteriophages that lyse bacterial strains of Pseudomonas aeruginosa . Ear drops were considered as a promising dosage form for instillation into the ear canal. Aim. The aim of the work is to develop a dosage form of Pseudomonas aeruginosa bacteriophages for the local treatment of infectious otitis media. Materials and Methods. The active substances of the developed drug are bacteriophages that lyse bacterial strains of Pseudomonas aeruginosa : PA5 and PA10, which were obtained by growing on a solid growth medium in mattress flasks with subsequent sterilizing filtration through a membrane filter (0,22 µm) and elimination of endotoxins on a chromatographic column. To obtain experimental compositions, excipients that do not cause a drop in the titer of bacteriophages were used – purified water as the solvent, viscosity modifiers: glycerol (CHIMMED, Russia) and a mix of macrogol 6 and glyceryl caprilocaprate brand Softigen 767 (Cremer, Germany), antioxidant Ethylenediaminetetraacetic acid (EDTA), preservatives nipagin and nipazole. The obtained samples were standardized according to pharmacopoeial indicators, recommended for the dosage form "drops" – density, pH, viscosity. For all experimental compositions, the stability of the titer of bacteriophages was studied by the Gratia method for 6 months. The local irritation and systemic effects were also studied on five chinchilla male rabbits. Results and discussion. As a result of the conducted research, four experimental compositions of ear drops with a cocktail of bacteriophages PA5 and PA10 were obtained. The optimal technological characteristics were observed in the composition containing glycerol as a viscosity modifier at a concentration of 10,0 %. For optimal composition, the stability of the bacteriophages cocktail titer, local irritating and systemic effects were analyzed. The study revealed stability of the bacteriophages PA5 and PA10 titers in the composition of dosage form, and absence of local irritating and systemic effects of ear drops. Conclusion. The dosage form can be recommended for preclinical studies.

Digital analysis is a method of assessing qualitative data by converting them into quantitative data using a personal computer’s graphics processing unit (GPU). Visual changes on the cervical surface in human papillomavirus (HPV)-associated pathology can be evaluated by extended colposcopy with a 3–5% acetic acid test and Schiller’s test. Acetowhite epithelium (appears after a test with acetic acid) in the form of flat condyloma is one of the main clinical manifestations of HPV infection (excluding manifestations on the metaplastic epithelium). The intensity of acetowhite epithelium (AWE) is a subjective parameter during gynecological examination, and to exclude the malignant process, a histology or liquid-based cytology should be performed. Objective assessment of the AWE intensity is introduced by digital image analysis using specialized software. The aim. To improve the assessment of visual changes of acetowhite epithelium on the cervical surface using a digital approach as an additional tool when performing extended colposcopy. Materials and methods. Colposcopy images of 359 patients were estimated by digital approach. Colposcopy images were made with a screenshot function after performing extended colposcopy. Screenshots of the cervix were converted to 8-bit type. This allowed us to estimate the intensity of AWE by software ImageJ. Index grey value (IndGV) was calculated to estimate the intensity of AWE. The IndGV data were assessed by MS office 365 (Excel v16.46) and RStudio v1.2.5042 statistical packages. Results and conclusion. The quantification approach detects the severity of AWE on the cervical surface. IndGV correlates with the grades of cervical intraepithelial neoplasia (CIN) and clinical manifestations of HPV. The clinical manifestations of HPV infection in CIN have a direct dependence on digital measurement as grey value (GV). These indicators give the opportunity to evaluate clinical manifestations in digital analysis in real-time mode, which does not require a significant financial investment. IndGV can be used as a prognostic factor of the severity of HPV infection and its clinical forms (CIN I–III and cervical cancer). Key words: digital medicine, quantitative approach, acetowhite epithelium, HPV infection

Antibiotic resistance represents an urgent and unresolved issue due to a rapid spread of multidrug-resistance organisms (MDROs). An alternative approach is the medical use of bacteriophages which have selective and lytic activity against specific bacterial strains, in contrast to broad-spectrum antibiotics. Isolation of bacteriophages is a multi-step, tedious, and labour-intensive technique, and physiology of various bacteriophages has been vaguely studied. These drawbacks hamper the flow production of bacteriophage preparations and require a stringent quality control. Here, we review the existing literature on genetically modified bacteriophages, in particular studies which examined efficacy of such bacteriophages for the treatment of multidrug-resistant infections. Genetically modified bacteriophages showed high efficiency in patients with multidrug-resistant infections applied either as a main treatment modality or as an adjuvant therapy added to the antibiotic treatment protocols. The key advantage of genetically modified bacteriophages is broader and higher lytic activity, as they can target antibiotic resistance genes such as efflux pumps, and low immunogenicity which delays their elimination by immune cells. We propose that genetically modified bacteriophages are able to overcome the shortcomings of natural bacteriophages and can be implemented for the prevention and treatment of bacterial infections, in particular those caused by MDROs.

Currently, the biological value of colostrum is generally considered as a resource of biotechnologies for the production of functional food products capable of purposefully improving the state of actual nutrition of certain categories of the population. At the same time, the use of essential micronutrients included in colostrum is significantly limited by the complexity of technological processes for the manufacture of biologically active additives based on a natural product. The article is devoted to the generalization and systematization of available information about the macronutrient composition of colostrum, the biological value of essential micronutrients included in the product, immunomodulatory, regulatory and prebiotic properties. The authors present examples of the use of colostrum and its fractions in the form of medicines and biologically active food additives. The possibilities of using a functional food product based on colostrum in industrial workers as a physiologically functional food ingredient with antioxidant effect, radioprotective properties, the possibility of neutralizing xenobiotics, binding heavy metals, arsenic compounds, cyanides, aromatic hydrocarbons are substantiated. The resource for information search is the bibliographic databases Medline and RSCI.

The presence of IgG and IgM antibodies in the venous blood of 76 patients with confirmed COVID-19 infection was determined by ELISA using Russian test systems. Different levels of IgM antibodies to N-protein and receptor binding domain of the Spike protein (RBD) were revealed. The dynamics of IgG antibodies to the whole virion antigen and recombinant antigens showed high values on weeks 4-5 of the disease. The level of IgG antibodies to Nprotein remained low throughout the observation period. The characteristic dynamics of IgG measured using test systems with sorbed whole virion or recombinant spike proteins reflects the duration of the disease.

The rapid increase in the incidence of multidrug-resistant pathogens poses an important task for the scientific community to find new ways to combat such pathogens. This increase is due to the widespread use of antibiotics of the main pharmacological groups for the treatment of infectious diseases against the backdrop of the ongoing COVID-19 epidemic. One of the promising directions in this area is bacteriophages due to their effectiveness against resistant pathogens and safety of use. Nevertheless, bacteriophages have a number of limitations that hinder their widespread use. In this regard, studies of endolysins - enzymes synthesized at the end of the lytic cycle of bacteriophages and destroying the bacterial cell wall - are being increasingly actively pursued. This article describes the characteristics of endolysins, their classification and advantages in comparison with antibiotics and bacteriophages. The descriptions of research carried out in the world in the field of obtaining endolysin preparations are given. Developments for the production of monoand combined endolysins for the treatment of a number of bacterial infections are described. The effectiveness of this approach for the treatment of infections, including those caused by multidrug-resistant pathogens, and the prospects for further work in this direction are shown. (English) [ABSTRACT FROM AUTHOR] Стремительный рост встречаемости полирезистентных возбудителей ставит перед научным сообществом важную задачу по по- иску новых путей борьбы с такими возбудителями. Этот рост обусловлен широким применением антибиотиков основных фарма- кологических групп для лечения инфекционных заболеваний на фоне не угасающей эпидемии COVID-19. Одним из перспектив- ных направлений в данной области являются бактериофаги ввиду своей эффективности в отношении резистентных возбудите- лей и безопасности применения. Тем не менее бактериофаги обладают рядом ограничений, затрудняющих их широкое приме- нение. В связи с этим все более активно ведутся исследования эндолизинов - ферментов, синтезирующихся в конце литическо- го цикла бактериофагов и разрушающих клеточную стенку бактерий. Дана характеристика эндолизинов, их классификация и описаны преимущества эндолизинов по сравнению с антибиотиками и бактериофагами. Приведены описания проводимых в ми- ре исследований в области получения препаратов эндолизинов. Рассмотрены разработки по получению моно- и комбинирован- ных эндолизинов для лечения ряда бактериальных инфекций. Показана эффективность данного подхода для лечения инфек- ций, в том числе вызванных полирезистентными возбудителями, и перспективность дальнейшей работы в этом направлении. (Russian) [ABSTRACT FROM AUTHOR] Copyright of Problems of Biological, Medical & Pharmaceutical Chemistry is the property of Russian Physician Public House Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The surface of the MA8 magnesium alloy, modified by laser treatment, was found to acquire superhydrophilic properties and high bactericidal activity against Escherichia coli K12 C600. The main mechanisms of bactericidal action were disruption of the integrity of the bacterial outer membrane, which was perforated by nanoparticles on a textured surface, and alkalization of the dispersion medium when it interacted with the metal. The proposed method opens up new prospects for metal protection against biocorrosion by creating superhydrophilic coatings with high bactericidal properties.

Our report concerns the observations made during the treatment of pneumonia with individually selected bacteriophages in HCAI patients on mechanical ventilation. 19 patients on mechanical ventilation whose condition was complicated by antibiotic-resistant pneumonia were examined. The treatment of patients was supplemented with phage therapy, bacteriophages were selected individually for each patient, taking into account the microbial etiology of the disease (Pseudomonas aeruginosa, Кlebsiella pneumoniae, Acinetobacter baumanii). Immunophenotyping of blood lymphocytes was carried out using 2-3-parameter flow cytometry. The functional activity of blood leukocytes was assessed by their ability to produce IFNα and IFNγ during cultivation. The level of interferons production in supernatants collected after cultivation was quantitatively evaluated both by their concentration (ELISA, reagents from “Vector-Best-Europe”, Russia) and by their biological activity. Statistical processing of the results was carried out using the Statistica 6 program according to the nonparametric Mann-Whitney U-test. In the course of successful phage therapy with individually selected bacteriophages overcoming of lymphopenia (if there was one) and an increase in both the number and functional activity of peripheral blood lymphocytes in all patients with pneumonia observed are noted. The relationship between the microbial load (mono- or mixed infection, the number of CFU pathogens of pneumonia, the need for repeated courses of phage therapy) and the degree of deficiency in one or another subpopulation of lymphocytes was not detected. Activation of the immune system achieved after one course of phage therapy was maintained for at least 3 weeks after phage administration was discontinued.