Olga V. Kisil

Invasive mycoses have become an increasingly serious global public health concern, particularly in immunocompromised patients. Species of the genus Aspergillus—most notably Aspergillus fumigatus—are among the principal causative pathogens. Despite advances in antifungal therapy, especially azole-based agents, the spread of azole-resistant Aspergillus spp. is emerging as a major clinical threat. This review summarizes current data on the prevalence of drug-resistant Aspergillus spp. and describes the resistance mechanisms identified to date. The primary focus is on publications from the last decade; however, key foundational studies from earlier periods were also considered. The scientific data search was performed in eLIBRARY.RU, PubMed, Google Scholar, and Wally. The analysis demonstrated a substantial increase in invasive aspergillosis cases caused by resistant Aspergillus strains. The main mechanisms of resistance include mutations in the cyp51 gene and hyperactivation of efflux transport proteins. Resistant isolates have been reported in Europe, Asia, Africa, and the Americas. These findings may be used to inform guidelines aimed at improving epidemiologic surveillance of antifungal resistance in Aspergillus. Priority areas for future research should include development of antifungal agents, improved diagnostic assays for rapid detection of resistant strains, and optimization of treatment regimens. There is an urgent need for greater clinician awareness regarding the risks associated with azole use and tighter antifungal resistance control measures.

Mycoses pose an increasing threat to public health, resulting in millions of invasive infections and a high mortality rate each year. The limited arsenal of antifungal agents, their toxicity, and the rapid spread of resistance underscore the urgent need for new therapeutic strategies. This review systematizes current trends in the development of antimycotic agents intended for the treatment of invasive mycoses. The primary focus is on drugs with novel mechanisms of action targeting key structures and metabolic pathways of the fungal cell. The emphasis is on publications from the past decade; however, significant fundamental research from earlier times has also been taken into account. The search was conducted in the electronic databases eLibrary.ru, PubMed, Google Scholar, and Wally. Promising approaches include inhibition of cell wall component synthesis, disruption of cell membrane function through effects on ergosterol, phospholipids, and sphingolipids, as well as effects on intracellular targets: fungal intracellular proteins and signaling pathways, protein biosynthesis processes, and nucleic acid replication and transcription. Agents inhibiting the synthesis of major cell wall components such as β-1,3-glucan (echinocandins, ibrexafungerpY), β-1,6-glucan, chitin (nikkomycin ZY), and GPI anchors (fosmanogepixY), are reviewed. Agents acting on ergosterol (oteseconazoleY, opelconazoleY), sphingolipids (IPC-synthase inhibitorsY), and phospholipids (mandimycinY) are analyzed. Fungal kinase inhibitors, Hsp90, calcineurin, N-myristoyltransferase, elongation factor EF-2, and nucleic acids (olorofimY) are described. Several of these compounds (olorofimY, fosmanogepixY, VT-1598Y, BSG005) are currently in clinical trials. The importance of identifying selective targets and developing combination therapy to overcome resistance and improve treatment effectiveness is emphasized. Y Hereafter, it means that the medicinal product is not registered in the Russian Federation.

Antibiotics, which evolved as a chemical weapon of some bacteria against others, are primarily known for their microbicidal and/or bacteriostatic effects; however, they also have numerous pleiotropic effects: anti-amyloid, anti-inflammatory, antioxidant, and anti-apoptotic. This review considers antibiotics with a translation-inhibiting mechanism of action, primarily tetracyclines, in the context of their non-antibiotic biological aspect, namely, the possibilities of supportive therapy for neurodegenerative diseases, as well as their antimitochondrial action and the mediated effect of aging cancellation.

Background. Invasive mycoses pose a growing health threat, especially for patients with weakened immune systems, whose number is increasing due to advances in oncology, transplantation, and intensive care. The limitations of existing antimycotics are their toxicity, narrow spectrum of action, low bioavailability, and growing resistance of pathogens. The slow pace of development of new antifungal agents compared to antibacterial ones exacerbates the situation, which makes the search for new effective and safe drugs critical. The aim of this review was to summarize and systematize information on current trends in the development of antimycotics, covering both the evolution of approaches to «classical» targets (cell wall, cell membrane) and strategies aimed at overcoming the current limitations of antifungal therapy. Methods. A systematic analysis of scientific literature and clinical research data was carried out using Google Scholar, eLibrary, PubMed, Wally, and ClinicalTrials.gov databases. The main focus was on the publications of the last decade, taking into account the key earlier studies. Results. Over the past 10 years, only 4 new drugs have entered clinical practice. There are 9 molecules in active clinical trials, including Gwt1 inhibitors, dihydroorotate dehydrogenases, and inhaled triazoles. Compounds with new mechanisms of action are of particular interest, for example, mandimycin, which targets phospholipids, inhibitors of inositol-phosphoceramide synthase, which is absent in humans. Conclusion. Despite the challenges associated with the eukaryotic nature of fungi, the development of new antimycotics continues in several promising areas focused on improving the properties of representatives of existing classes, as well as searching for fundamentally new targets.

The chemical modifications of DNA are of pivotal importance in the epigenetic regulation of cellular processes. Although the function of 5-methylcytosine (5mC) has been extensively investigated, the significance of 5-hydroxymethylcytosine (5hmC) has only recently been acknowledged. Conventional methods for the detection of DNA methylation frequently lack the capacity to distinguish between 5mC and 5hmC, resulting in the combined reporting of both. The growing importance of 5hmC has prompted the development of a multitude of methods for the qualitative and quantitative analysis of 5hmC in recent years, thereby facilitating researchers’ understanding of the mechanisms underlying the onset and progression of numerous diseases. This review covers both established and novel methods for the detection of cytosine modifications, including 5mC, 5hmC, 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC), with a particular focus on those that allow for accurate mapping and detection, particularly with third-generation sequencing. The review aims to help researchers choose the most appropriate methods based on their specific research goals and budget.

Serious work is being carried out in the world in the field of combating antibiotic resistance: reducing the prescribing of antibiotics, banning the use of antibiotics as stimulators of animal growth, improving infection control. Antimicrobial resistance is systematically monitored not only in every medical center, but also at the national level. The collected data is successfully used to implement local and national recommendations on the optimal use of antibiotics.

In this review, the current information about surfactin (a cyclic lipopeptide), which is one of the most studied microbial biosurfactants, is summarized and analyzed. The mechanism of surfactin biosynthesis, the spectrum of its natural and synthetic isoforms, the biological activity of surfactin, as well as its role in the regulation of the vital processes of producers, have been presented. The potential of using surfactin and biopreparations based on surfactin-producing bacteria of the genus Bacillus to protect and stimulate plant immunity has been shown.

Medicinal probiotic Sporobacterin is based on the Bacillus subtilis 534 strain, which has been shown to have antimicrobial activity against many bacteria, both the collection strains and the antibiotic-resistant forms of clinical isolates of pathogenic bacteria and fungi. Considering this strain as an antibiotic producer, a step-by-step mutagenic treatment was carried out in order to obtain a variant that consistently exhibits a certain high-level antibiotic activity. A mutant variant was obtained during the three stages of mutagenic treatment and selection; it effectively suppresses the growth of pathogenic staphylococci, including methicillin-resistant staphylococcus (MRSA).

The epidemiological surveillance of listeriosis remains an urgent problem for Russia, especially in the metropolitan areas. The Gram-positive bacterium Listeria monocytogenes, which causes the infectious disease listeriosis, is a foodborne pathogen and widespread in nature. Ready-to-eat foods are particularly dangerous because no heat treatment or other antimicrobial action is performed between their production and consumption. Newborns, pregnant women, the elderly, and immunocompromised people are highly susceptible to listeriosis. The timely detection of L. monocytogenes in foodstuffs during the manufacturing and storage phases is important both for food processing and catering companies and for public health.

This article reviews the existing approaches to determining the TERT promoter mutational status in patients with various tumoral diseases of the central nervous system. The operational characteristics of the most common methods and their transferability in medical practice for the selection or monitoring of personalized treatments based on the TERT status and other related molecular biomarkers in patients with the most common tumors, such as glioblastoma, oligodendroglioma, and astrocytoma, are compared. The inclusion of new molecular markers in the course of CNS clinical management requires their rapid and reliable assessment. Availability of molecular evaluation of gliomas facilitates timely decisions regarding patient follow-up with the selection of the most appropriate treatment protocols. Significant progress in the inclusion of molecular biomarkers for their subsequent clinical application has been made since 2016 when the WHO CNS classification first used molecular markers to classify gliomas. In this review, we consider the methodological approaches used to determine mutations in the promoter region of the TERT gene in tumors of the central nervous system. In addition to classical molecular genetical methods, other methods for determining TERT mutations based on mass spectrometry, magnetic resonance imaging, next-generation sequencing, and nanopore sequencing are reviewed with an assessment of advantages and disadvantages. Beyond that, noninvasive diagnostic methods based on the determination of the mutational status of the TERT promoter are discussed.