BACKGROUND: Wastewater resistome surveillance has emerged as a promising strategy for monitoring antimicrobial resistance (AMR) at the population level. However, translating complex environmental resistome datasets into operational indicators of resistance risk remains a major challenge because standardized frameworks capable of integrating ecological, genetic, and environmental determinants of AMR are lacking. OBJECTIVE: To propose the Resistome Risk Index (RRI), a conceptual framework for transforming wastewater resistome data into standardized indicators of antimicrobial resistance risk suitable for longitudinal and comparative surveillance. METHODS: The proposed framework integrates multiple surveillance layers, including antimicrobial resistance gene abundance, mobility potential, host association, temporal persistence, and environmental context, into a composite resistome risk indicator. It combines targeted molecular monitoring, metagenomic analyses, and environmental metadata within a unified analytical architecture linking microbial community composition, mobilome dynamics, and resistome structure. Methodological challenges associated with host attribution, mobility inference, and ecological background variation are also discussed. RESULTS: The proposed RRI framework integrates diverse wastewater surveillance datasets into a standardized conceptual architecture that captures the ecological structure and dissemination potential of antimicrobial resistance. The framework supports longitudinal monitoring, inter-site comparisons, and integration of wastewater surveillance into One Health AMR monitoring programs. CONCLUSION: The RRI represents a theory-driven framework for translating wastewater resistome measurements into operational indicators of resistance risk. Although the framework requires empirical validation and calibration using longitudinal and multicenter datasets before practical implementation, it provides a scalable foundation for the development of predictive wastewater resistome surveillance systems and standardized antimicrobial resistance risk assessment.
BACKGROUND: Gram-positive cocci, particularly Staphylococcus aureus and Staphylococcus epidermidis , are common components of the human microbiota but can act as opportunistic pathogens, causing a wide range of infections. The increasing prevalence of antimicrobial resistance has highlighted the urgent need for alternative preventive strategies, including effective preventive vaccines. However, despite extensive research, no approved vaccines against these pathogens are currently available. OBJECTIVE: To evaluate the role of reverse vaccinology in identifying potential vaccine antigens for the prevention of infections caused by S. aureus and S. epidermidis . METHODS: This review examines current antigen discovery approaches based on whole-genome sequencing, comparative genomics, and reverse vaccinology. Relevant literature on antigen discovery, genetic diversity, and vaccine candidate identification was examined, with a focus on conserved and infection-specific targets. RESULTS: Genomic approaches enable the identification of novel antigenic targets and provide insights into pathogen diversity and virulence mechanisms. Reverse vaccinology has facilitated the identification of conserved surface proteins and virulence- associated factors as promising targets for vaccine development. However, most vaccine candidates remain at the preclinical stage and their protective efficacy as well as immunogenicity of vaccine targets require further validation. CONCLUSION: Reverse vaccinology represents a promising platform for accelerating antigen discovery and improving vaccine design against staphylococcal infections. Integration of genomic, proteomic, and immunological data, combined with rigorous experimental and clinical validation, is essential to overcome current challenges and advance the development of effective vaccines.
BACKGROUND: Bacterial vaginosis (BV) is a common vaginal dysbiosis characterized by loss of Lactobacillus -dominant communities and overgrowth of anaerobic bacteria. BV is highly prevalent in sub-Saharan Africa and is linked to adverse pregnancy outcomes and heightened susceptibility to sexually transmitted infections (STIs), including Human Immunodeficiency Virus (HIV). OBJECTIVE: To synthesize current evidence on BV epidemiology in West Africa, microbiome-based mechanisms, risk factors, diagnostic approaches under resource constraints, clinical consequences, and management strategies including emerging microbiome-directed interventions. METHODS: This narrative review synthesized peer-reviewed literature and guideline documents on BV in West Africa. Comprehensive searches were conducted in PubMed, Scopus, and Google Scholar. Studies published between 2020–2024 were prioritized; earlier seminal works were retained to explain diagnostic criteria and pathogenesis. Studies were included if they reported human data from West African populations on BV prevalence, microbiome mechanisms, or clinical outcomes. RESULTS: BV pathogenesis is increasingly understood as a polymicrobial biofilm-associated dysbiosis in which Gardnerella spp. play a central structural role, supporting persistence and recurrence. Diagnostic reliance on syndromic management in many settings may lead to misclassification and inadequate follow-up. Standard nitroimidazole or clindamycin regimens offer good short-term response, yet recurrence remains common, motivating interest in adjunctive strategies such as probiotic Lactobacillus preparations and experimental vaginal microbiota transplantation (VMT). Evidence also supports the importance of considering sexual partnership dynamics in recurrence pathways. CONCLUSION: BV represents a major but under-addressed reproductive health challenge in West Africa. Strengthening microscopy-based diagnosis, integrating BV into antenatal and STI services, addressing intravaginal practices, and evaluating microbiome-restorative interventions in African populations are priorities for reducing BV-associated morbidity.
BACKGROUND: Cystic echinococcosis, caused by Echinococcus granulosus , remains a significant zoonotic infection in endemic regions. Although hepatic involvement is the most common presentation, rare extrahepatic intra-abdominal localizations, such as primary mesenteric hydatid cysts, pose diagnostic and surgical challenges. OBJECTIVE: To describe the clinical, radiological, surgical, and histopathological features of three cases of hydatid disease, including a rare primary mesenteric cyst, and to analyze their diagnostic and management implications in endemic settings. METHODS: This study retrospectively evaluated three cases of hydatid disease diagnosed at the Department of Microbiology, Indira Gandhi Government Medical College and Hospital, Nagpur, India, between January and December 2025. Clinical presentation, imaging findings, operative details, and histopathological results were analyzed. RESULTS: Two patients presented with hepatic hydatid cysts, while one patient had a primary mesenteric cyst without hepatic involvement. Imaging revealed well-defined cystic lesions consistent with a hydatid disease. Histopathology confirmed the diagnosis in all cases by demonstrating laminated membranes and protoscolices/hooklets in the cyst. Surgical excision was performed in all patients, followed by administration of albendazole therapy. No immediate postoperative complications were noted. The follow-up duration was three months, and no recurrence was reported. CONCLUSION: Hydatid disease should remain a key differential diagnosis for cystic intra-abdominal lesions in endemic regions. Rare extrahepatic sites, such as the mesentery, require heightened clinical suspicion. Combined surgical and antiparasitic management remains effective; however, careful intraoperative handling is essential to prevent dissemination.
BACKGROUND: The oral microbiota is a complex, site-specific microbial ecosystem that develops from birth and contributes to oral homeostasis, immune maturation, and host – microbe interactions. Increasing evidence links oral dysbiosis not only to dental caries and periodontal disease but also to selected extra-oral conditions, particularly in children. OBJECTIVE: To summarize recent evidence on the development and variability of the oral microbiota across the lifespan and to describe reported associations between oral microbial shifts and diseases of the oropharynx and other organ systems, with particular emphasis on pediatric populations. METHODS: A narrative synthesis was performed using domestic and international publications from the past decade, including peer-reviewed original studies, systematic reviews, and meta-analyses. Evidence was interpreted with attention to study design, sampling sites (saliva, plaque, and mucosal niches), population characteristics, and microbiota profiling methods, including culture-based approaches, 16S rRNA gene sequencing, and metagenomic techniques. RESULTS: Oral microbial communities differ by oral niche and change dynamically with age, dentition, diet, hygiene practices, host factors, and clinical status. Early-life colonization and tooth eruption shape microbiota maturation, and pediatric studies consistently report associations between oral dysbiosis and recurrent oropharyngeal infections and inflammatory conditions. Across studies, heterogeneity in sampling strategies, analytical pipelines, and cohort composition limits comparability and constrains causal inference. CONCLUSION: Oral microbiota profiling — particularly saliva- and plaque-based signatures — shows potential for risk stratification and monitoring of selected oral and systemic conditions. However, well-designed longitudinal studies and interventional trials are required to validate clinically useful biomarkers and to clarify causal mechanisms linking oral dysbiosis to disease.
INTRODUCTION: Antimicrobial resistance (AMR) remains a critical global health challenge and is increasingly reported in bacteria circulating among healthy young adults. University students constitute one of the key community groups in which antibiotic misuse and environmental exposures can drive the emergence and dissemination of resistant bacteria. OBJECTIVES: This study investigated the prevalence and resistance patterns of Escherichia coli isolates circulating among university students in Southwestern Nigeria, with a focus on multidrug resistance (MDR) and extended-spectrum β-lactamase (ESBL) production in these bacteria. METHODS: A cross-sectional study was conducted among 200 volunteer undergraduate students. Standard microbiological methods were used for the collection, purification, and identification of fecal E. coli isolates, followed by antimicrobial susceptibility testing according to established protocols. ESBL production was phenotypically screened and genotypically confirmed by polymerase chain reaction (PCR) targeting bla TEM , bla SHV , and bla CTX-M genes. Potential behavioral and environmental risk factors for carriage of MDR bacteria by students were assessed using structured questionnaires. Descriptive and inferential statistical analyses were performed, with a significance threshold of p < 0.05. RESULTS: A total of 350 E. coli isolates were recovered from 186 students. Resistance to tetracycline was the most prevalent (90.6%) among E. coli isolates, whereas meropenem exhibited the lowest resistance rate (2.8%). Overall, 84.9% of the isolates demonstrated multidrug resistance. Twenty isolates (5.7%) were phenotypically identified as ESBL producers, and 18 (5.1%) harbored at least one of the target genes. Carriage of MDR E. coli by university students was significantly associated with self-medication, while the use of well or rainwater as drinking sources was significantly associated with carriage of ESBL-producing bacteria (p < 0.05). CONCLUSION: This study demonstrates high burden of AMR among commensal E. coli isolates from university students, particularly resistance to tetracycline. The circulation of MDR and ESBL-producing strains among students highlights the combined influence of their inappropriate antibiotic use and environmental exposure. Strengthened AMR education, antibiotic regulation, and water and sanitation infrastructure within university settings is essential to limit the spread of bacterial resistance.
BACKGROUND: Enterococci, commonly found in the gastrointestinal, biliary, and genitourinary tracts, are increasingly implicated in a wide range of clinical infections worldwide. Although E. faecalis and E. faecium account for the majority of enterococcal infections, diseases caused by emerging Enterococcus spp. are being reported with increasing frequency and are often associated with higher levels of antimicrobial resistance. OBJECTIVE: This study aimed to investigate vancomycin resistance patterns among various Enterococcus spp. isolated from clinical specimens. MATERIALS AND METHODS: This cross-sectional study was conducted at a tertiary care hospital in Nagpur, India, and analyzed vancomycin resistance patterns among 224 Enterococcus isolates obtained from 17,231 clinical specimens collected over a two-year period. Species identification was performed using standard microbiological methods. Antimicrobial susceptibility testing was carried out in accordance with the Clinical and Laboratory Standards Institute (CLSI) 2024 guidelines, with particular emphasis on vancomycin resistance. RESULTS: E. faecium was the most frequently isolated species. UTIs were the most common clinical presentation, followed by bacteremia and wound infections. We observed high resistance rates for penicillin (81.2%) and ampicillin (64.7%), along with high-level gentamicin resistance (58.5%). Vancomycin resistance was detected in 14.3% of the isolates, with significantly higher resistance observed in E. faecium than in other species (p < 0.05). Linezolid resistance was identified in 5.8% of the isolates. Although less frequently isolated, non- E. faecium and non- E. faecalis strains demonstrated notable resistance to multiple antimicrobial agents. CONCLUSIONS: The emergence of vancomycin resistance across diverse Enterococcus spp. highlights the importance of routine species-level identification and comprehensive antimicrobial susceptibility testing. Judicious antibiotic use, coupled with stringent infection prevention and control measures, is essential to limit the dissemination of multidrug-resistant enterococci.
Glioblastoma remains a tumor with one of the most unfavorable prognoses in clinical oncology. Given the insufficient effectiveness of standard treatment modalities, oncolytic virotherapy is being actively developed. However, the influenza virus has so far remained on the periphery of scientific attention. In this review, we outline the key characteristics and features of gliomas that determine their resistance to therapy; examine the immunosuppressive microenvironment and strategies for its modulation; summarize the status of clinical trials and preclinical development of viral agents for glioma therapy; and identify promising targets for combination approaches. Attention is paid to the potential of influenza-based vectors as oncolytic agents, with consideration of both the advantages and possible limitations of this platform.
ВВЕДЕНИЕ: UniFluVec — живая аттенуированная рекомбинантная вакцина против гриппа, разработанная для усиления мукозального иммунитета и формирования широкого перекрестного иммунного ответа при интраназальном введении. В данном рандомизированном двойном слепом плацебо-контролируемом клиническом исследовании фазы 1 мы оценили ее безопасность и переносимость у здоровых взрослых добровольцев. МЕТОДЫ: В исследование были рандомизированы 60 добровольцев в возрасте 18–49 лет, которые получали две дозы вакцины UniFluVec интраназально (6.7 или 7.7 log 10 ЭИД 50 ) либо плацебо с интервалом 21 день. Оценка безопасности включала анализ местной и системной реактогенности, регистрацию незапланированных нежелательных явлений (НЯ), серьезных нежелательных явлений (СНЯ), клинико-лабораторных показателей, жизненно важных функций, а также оценку вирусовыделения с использованием экспресс-теста на антиген вируса. РЕЗУЛЬТАТЫ: Вакцина UniFluVec хорошо переносилась при обоих уровнях дозирования. Связанных с вакцинацией СНЯ или клинически значимых сигналов безопасности выявлено не было. Наиболее часто регистрировались легкие местные реакции, преимущественно заложенность носа, ринорея и боль в горле, которые проходили самостоятельно. Системные симптомы, включая субфебрильную температуру, головную боль, утомляемость и миалгию, наблюдались редко, носили кратковременный характер и в большинстве случаев были легкой степени выраженности. Связанных с вакцинацией отклонений гематологических, биохимических показателей или показателей жизненно важных функций не выявлено. Согласно данным экспресс-тестирования, вирус гриппа A не был обнаружен ни у одного добровольца, ни на одном визите исследования. Усиления реактогенности после введения второй дозы не отмечалось. ЗАКЛЮЧЕНИЕ: Вакцина UniFluVec продемонстрировала благоприятный профиль безопасности и переносимости у здоровых взрослых добровольцев, при отсутствии клинически значимых нежелательных явлений. Полученные результаты подтверждают целесообразность дальнейшей клинической разработки UniFluVec в качестве кандидата универсальной вакцины против гриппа.
Глиобластома остается опухолью с одним из самых неблагоприятных прогнозов в клинической онкологии. На фоне недостаточной эффективности стандартных методов лечения активно развивается онколитическая виротерапия. Однако вирус гриппа все еще остается на периферии внимания. В данный обзор мы включили ключевые характеристики и особенности глиом, определяющие резистентность к терапии; рассмотрели иммуносупрессивное микроокружение и стратегии его коррекции; обобщили текущий статус клинических исследований и доклинических разработок вирусных препаратов для терапии глиом и выделили перспективные точки приложения для комбинированных подходов. Особое внимание мы уделили потенциалу гриппозных векторов как онколитических агентов, рассматривая преимущества и возможные ограничения этой платформы.
BACKGROUND: UniFluVec is a live attenuated recombinant influenza vaccine candidate designed to enhance mucosal immunity and provide broad cross-protective responses after intranasal administration. This Phase 1 randomized, double-blind, placebo-controlled trial evaluated its safety and tolerability in healthy adults. METHODS: Sixty volunteers aged 18-49 years were randomized to receive two intranasal doses of UniFluVec (6.7 or 7.7 log10EID50) or placebo, administered 21 days apart. Safety assessments included local and systemic reactogenicity, unsolicited adverse events (AEs), serious AEs (SAEs), clinical laboratory parameters, vital signs, and evaluation of viral shedding using rapid antigen testing. RESULTS: UniFluVec was well tolerated at both dose levels. No vaccine-related SAEs or clinically significant safety signals were observed. The most frequently reported adverse events were mild local reactions – primarily nasal congestion, rhinorrhea, and sore throat – which resolved spontaneously. Systemic symptoms, including low-grade fever, headache, fatigue, and myalgia, were infrequent, transient, and predominantly mild. No vaccine-related abnormalities were detected in the hematological, biochemical, or vital-sign parameters. No influenza A virus was detected in any volunteer at any study visit according to the express test results. The reactogenicity did not increase after the second dose. CONCLUSION: UniFluVec demonstrated a favorable safety and tolerability profile in healthy adults, with no clinically meaningful adverse events reported. These findings support the further clinical development of UniFluVec as a universal influenza vaccine candidate. Clinical Trial Registration number: NCT04650971 (2020-12-03).
Artificial intelligence (AI) is reshaping microbiology laboratories by improving diagnostic accuracy, workflow efficiency, and the interpretation of increasingly complex datasets. Machine learning algorithms enhance microbial identification, particularly when applied to MALDI-TOF MS spectral analysis, and support early prediction of antimicrobial resistance through genomic modelling. AI-driven image analysis accelerates microscopic detection of pathogens and reduces operator variability. In metagenomics, AI enables high-resolution profiling of microbial communities and reveals novel associations with human disease. Despite challenges involving data quality, validation, ethics, and regulatory oversight, AI’s integration into microbiology promises substantial gains in precision diagnostics, antimicrobial stewardship, and research capability.
About one third of all Gram-negative bacterial infections globally are caused by Klebsiella pneumoniae. These bacteria readily become drug resistant and form biofilms that significantly complicates treatment of infections. This study aimed to compare biofilm production in carbapenem-resistant (CR) and carbapenem-susceptible (CS) Klebsiella pneumoniae strains and to evaluate the association between biofilm production, carbapenem resistance and the presence of virulence genes mrkA , wbbM , wzm , luxS implicated in biofilm formation. A total of 37 CR and 63 CS K. pneumoniae isolates were included in the study. Antibiotic susceptibility testing was performed using an automated Vitek 2 system. The presence of virulence genes ( mrkA , wbbM , wzm , luxS ) was investigated by PCR. Biofilm formation was assessed using the spectrophotometric microplate method. Overall, 65% of isolates were multidrug-resistant (MDR). The carbapenem resistance rate was 37%. CR strains showed significantly higher resistance to multiple antibiotics compared with CS strains. Biofilm production was detected in 76% of all isolates: 100% of CR strains and 61.9% of CS strains. The most frequently detected gene was mrkA (73%), followed by wbbM (57%), luxS (52%), and wzm (32%). MDR rates were higher in CR strains and in isolates with biofilm production. MIC values for ertapenem, meropenem, amikacin, piperacillin-tazobactam, cefoxitin, ceftazidime, and ceftriaxone were higher in biofilm-producing strains. Biofilm production was statistically significantly associated with MDR and strongly associated with carbapenem resistance, whereas the presence of individual virulence genes did not show any statistically significant association with it.
INTRODUCTION: Hydrocephalus is characterized by the abnormal accumulation of cerebrospinal fluid (CSF) within the brain, resulting in elevated intracranial pressure. A ventriculoperitoneal (VP) shunt diverts excess CSF to the peritoneal cavity to relieve this pressure. However, VP shunt placement carries a significant risk of device-related infection, most of which occur within the first three months after surgery. The recent emergence of multidrug-resistant pathogens has heightened concerns, likely reflecting widespread and sometimes inappropriate antibiotic use. OBJECTIVE: To characterize the microbiological profile and antimicrobial resistance patterns of VP shunt infections, with the goal of informing the hospital’s antibiotic stewardship policy. METHODS: A single-center prospective observational cohort study was conducted from February to July 2024. Cerebrospinal fluid samples were aseptically collected from VP shunt chambers and by shunt tapping and cultured using standard microbiological techniques. Antimicrobial susceptibility was assessed using Kirby–Bauer disc diffusion method and interpreted according to the 2024 CLSI guidelines. Statistical significance was evaluated using the Chi-square and Fisher’s exact tests. RESULTS: VP shunt infection occurred in 44.4% of the cases. The most frequently isolated organisms were Klebsiella pneumoniae (16.7%), Acinetobacter species (9.3%), and Escherichia coli (7.4%); Burkholderia cepacia and Staphylococcus aureus were each detected in 1.9% of the cases. Gram-negative isolates exhibited higher antimicrobial resistance than Gram-positive organisms. Re-shunting was required in 31.5% of patients, and the overall mortality rate was 14.8%. CONCLUSIONS: This study revealed an alarmingly high (44.4%) infection rate accompanied by substantial antimicrobial resistance. Rigorous aseptic techniques, early diagnosis, prompt targeted therapy, and strict adherence to antimicrobial stewardship protocols are essential to reduce morbidity and mortality associated with VP shunt infections.
BACKGROUND: Dichrostachys cinerea , a plant known for its extensive use in traditional medicine. OBJECTIVE: D. cinerea was analyzed to identify its bioactive compounds and to assess its therapeutic potential. METHODS: Using gas chromatography – mass spectrometry (GC-MS) and column chromatography, we identified and characterized the chemical constituents of D. cinerea , shedding light on their potential health benefits. The separation and purification of a variety of compounds were performed by column chromatography, while GC-MS allowed for detailed structural analysis of these bioactive components. RESULTS: Our findings mark significant progress in the study of the chemical composition of D. cinerea , emphasizing its potential applications in pharmaceutical and medicinal fields. The identified compounds possessed useful pharmacological properties, including antioxidant, anti-inflammatory, and antimicrobial activities. Obtained data significantly advances our understanding of the plant’s bioactive properties and provides a foundation for future studies exploring its therapeutic potential. CONCLUSION: The outcomes of this study have implications for the development of novel drugs and herbal remedies, underscoring the importance of D. cinerea as a valuable resource in the quest for new medicines.
INTRODUCTION: Escherichia coli , Pseudomonas aeruginosa , and Klebsiella oxytoca are among the most frequently isolated pathogens implicated in human disease in Burkina Faso. In addition, the emergence of carbapenem-resistant E. coli , P. aeruginosa , and K. oxytoca due to the production of IMP and VIM enzymes and the spread of these bacteria is a real concern for health facilities. However, the coexistence of the resistance genes encoding these enzymes in clinical bacterial isolates from Burkina Faso has not been previously reported. OBJECTIVE: To prove the coexistence of VIM and IMP in E. coli , P. aeruginosa and K. oxytoca clinical isolates from two medical centers in Ouagadougou, Burkina Faso, by means of conventional PCR. METHODS: Antibiotic susceptibility testing of 158 gram-negative bacilli isolates was performed against carbapenems and aztreonam using the disk diffusion method. The resistant isolates were screened using conventional polymerase chain reaction for the bla VIM and bla IMP genes. RESULTS: E. coli (45.1%, 41 isolates) was the most common among the resistant species, with a higher level of resistance to ertapenem (20.9%, 19 isolates) from all the carbapenems. P. aeruginosa (9.9%, 9 isolates) and K. oxytoca (1.1%, one isolate) were less common resistant species. The genes bla VIM and bla IMP were detected simultaneously in only 5.5% (5 isolates) of the resistant bacterial strains, including three strains of E. coli , one strain of P. aeruginosa , and one strain of K. oxytoca . CONCLUSION: This study established the coexistence of bla VIM and bla IMP genes in E. coli , P. aeruginosa , and K. oxytoca strains isolated from patients at the Centre Hospitalier Universitaire de Tengandogo and the Hôpital Saint Camille de Ouagadougou in Burkina Faso. These bacterial isolates were resistant to carbapenems due to the production of VIM and IMP enzymes.
OBJECTIVE OF THE STUDY: This review analyzes the epidemiological situation of fungal and bacterial infections in Russia, including the identification of priority pathogens based on WHO data, their geographic distribution, impact on various age or social groups, and infection severity. The analysis covers the dynamics of infection prevalence over the past 10 years. Additionally, it examines the impact of the identified trends on population morbidity, mortality, and disability rates. DATA SOURCES AND ANALYSIS: The analysis was based on official statistics from Federal Service for the Oversight of Consumer Protection and Welfare (FSOCPW, Russia), information from the WHO, and data from papers published in peer-reviewed scientific journals. It considers population morbidity and mortality rates together with factors influencing the spread of infections, namely, changes in virulence, development of antibiotic resistance, spread of resistant strains, and emerging pathogens. The data used for the assessment of infectious disease dynamics over the past 10 years also include such factors as climate change, urbanization, and migration, together with the geographic distribution of infectious diseases and their demographic impact. CONCLUSION: The results highlight the need for continuous epidemiological monitoring, development of new strategies for the prevention and treatment of infectious diseases and strengthening of measures to combat antibiotic resistance in Russia.
ЦЕЛЬ ИССЛЕДОВАНИЯ: Данная обзорная статья анализирует эпидемиологическую ситуацию по грибковым и бактериальным инфекциям в России, включая идентификацию приоритетных возбудителей с учетом данных ВОЗ, их географическое распространение, влияние на различные возрастные и социальные группы, а также тяжесть инфекций. Анализ охватывает динамику распространенности за последние 5-10 лет, учитывая изменения вирулентности, антибиотикорезистентность, новые патогены и такие факторы, как климатические изменения, применение антибиотиков, урбанизация и миграция, а также влияние выявленных тенденций на заболеваемость, смертность и инвалидизацию. ИСТОЧНИКИ ДАННЫХ: Анализ основан на данных официальной статистики Роспотребнадзора, информации ВОЗ, публикациях, цитируемых в базах данных PubMed и Scopus, а также в других рецензируемых научных журналах. Рассматриваются данные о заболеваемости, смертности, резистентности к противомикробным препаратам и факторах, влияющих на распространение инфекций. ЗАКЛЮЧЕНИЕ: Полученные результаты демонстрируют необходимость постоянного эпидемиологического мониторинга, разработки новых стратегий профилактики и лечения инфекционных заболеваний и усиления мер по борьбе с антибиотикорезистентностью в России.
INTRODUCTION: Oncolytic viruses are a promising approach for treating malignant brain tumors as part a of combination therapy. OBJECTIVE: To develop reporter influenza A viruses expressing NanoLuc luciferase and evaluate their safety following intracranial administration in rats. METHODS: Chemiluminescent reporter influenza A virus strains were obtained by reverse genetics. The NS genetic segment of the T_NS124-Luc and E_NS124-Luc strains encoded a fusion protein that combined NS1 124 and NanoLuc. In the T_NS124-2A-Luc and E_NS124-2A-Luc strains, the NS1 124 and NanoLuc sequences were separated by a 2A co-translational cleavage site. To enhance the tumor specificity of the viruses, the trypsin cleavage site (T) in the hemagglutinin (HA) protein was replaced with an elastase cleavage site (E) by introducing S342→P and R343→I substitutions in the HA region of the E_NS124-Luc and E_NS124-2A-Luc constructs. RESULTS: The obtained constructs demonstrated comparable reproductive and luminescent activity in MDCK cells. However, vectors containing the 2A site upstream of the transgene infected the glioma cell lines C6, A172, and T98G more effectively. Intracranial administration of a high dose of the virus was safe, causing no neurological or other pathological symptoms in rats. In addition, the luminescent reporter NanoLuc was expressed at the injection site without the formation of active viral progeny. CONCLUSION: This study demonstrated that a chemiluminescent influenza A virus strain can induce transgene expression at the site of intracranial injection without active viral replication.
