Publications by authors named "Usachev E"

The combined or multivalent vaccines are actively used in pediatric practice and offer a series of advantages, including a reduced number of injections and visits to the doctor, simplicity of the vaccination schedule and minimization of side effects, easier vaccine monitoring and storage, and lower vaccination costs. The practice of widespread use of the combined vaccines has shown the potential to increase vaccination coverage against single infections. The mRNA platform has been shown to be effective against the COVID-19 pandemic and enables the development of combined vaccines.

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Article Synopsis
  • A limited number of innovative antibacterial agents are being developed to effectively target critical Gram-negative bacteria resistant to current treatments, with endolysins showing promise due to their unique action against these pathogens.
  • The study uses a multidisciplinary approach including genetic engineering, structural analysis, and various formulations of the engineered endolysin LysECD7-SMAP, which are tested for effectiveness in preclinical models of infections such as sepsis and pneumonia.
  • Results indicate that LysECD7-SMAP is effective against multiple drug-resistant bacteria, and in vivo studies confirm the efficacy of its formulated dosage forms, along with insights into how it interacts with bacterial cell walls.
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Antibacterial therapy with phage-encoded endolysins or their modified derivatives with improved antibacterial, biochemical and pharmacokinetic properties is one of the most promising strategies that can supply existing antibacterial drugs array. Gram-negative bacteria-induced infections treatment is especially challenging because of rapidly spreading bacterial resistance. We have developed modified endolysin LysECD7-SMAP with a significant antibacterial activity and broad spectra of action against gram-negative bacteria.

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Seasonal influenza remains a serious global health problem, leading to high mortality rates among the elderly and individuals with comorbidities. Vaccination is generally accepted as the most effective strategy for influenza prevention. While current influenza vaccines are effective, they still have limitations, including narrow specificity for certain serological variants, which may result in a mismatch between vaccine antigens and circulating strains.

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The ability of most opportunistic bacteria to form biofilms, coupled with antimicrobial resistance, hinder the efforts to control widespread infections, resulting in high risks of negative outcomes and economic costs. Endolysins are promising compounds that efficiently combat bacteria, including multidrug-resistant strains and biofilms, without a low probability of subsequent emergence of stable endolysin-resistant phenotypes. However, the details of antibiofilm effects of these enzymes are poorly understood.

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SARS-CoV-2 variants have evolved over time in recent years, demonstrating immune evasion of vaccine-induced neutralizing antibodies directed against the original S protein. Updated S-targeted vaccines provide a high level of protection against circulating variants of SARS-CoV-2, but this protection declines over time due to ongoing virus evolution. To achieve a broader protection, novel vaccine candidates involving additional antigens with low mutation rates are currently needed.

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RNA interference (RNAi)-based therapeutics hold the potential for dominant genetic disorders, enabling sequence-specific inhibition of pathogenic gene products. We aimed to direct RNAi for the selective suppression of the heterozygous c.607 G > A variant causing encephalopathy.

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Tick-borne encephalitis virus (TBEV) is one of the most threatening pathogens which affects the human central nervous system (CNS). TBEV circulates widely in Northern Eurasia. According to ECDC, the number of TBE cases increase annually.

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Single-domain antibodies (sdAbs, VHHs, or nanobodies) are a promising tool for the treatment of both infectious and somatic diseases. Their small size greatly simplifies any genetic engineering manipulations. Such antibodies have the ability to bind hard-to-reach antigenic epitopes through long parts of the variable chains, the third complementarity-determining regions (CDR3s).

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Approximately 1/6 of humanity is at high risk of experiencing cholera epidemics. The development of effective and safe vaccines against the primary cause of cholera, is part of the public health measures to prevent cholera epidemics. Natural nontoxigenic isolates represent a source of new genetically improved and relatively safe vaccine strains.

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Endolysin-based therapeutics are promising antibacterial agents and can successfully supplement the existing antibacterial drugs array. It is specifically important in the case of Gram-negative pathogens, e.g.

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The use of recombinant endolysins is a promising approach for antimicrobial therapy capable of counteracting the spread of antibiotic-resistant strains. To obtain the necessary biotechnological product, diverse peptide tags are often fused to the endolysin sequence to simplify enzyme purification, improve its ability to permeabilize the bacterial outer membrane, etc. We compared the effects of two different types of protein modifications on endolysin LysECD7 bactericidal activity in vitro and demonstrated that it is significantly modulated by specific permeabilizing antimicrobial peptides, as well as by widely used histidine tags.

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The extremely rapid spread of multiple-antibiotic resistance among Gram-negative pathogens threatens to move humankind into the so-called "post-antibiotic era" in which the most efficient and safe antibiotics will not work. Bacteriophage lysins represent promising alternatives to antibiotics, as they are capable of digesting bacterial cell wall peptidoglycans to promote their osmotic lysis. However, relatively little is known regarding the spectrum of lysin bactericidal activity against Gram-negative bacteria.

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It was shown that full-length virion RNA of segment 8 of influenza virus A/Aichi/2/68 (H3N2) can initiate the synthesis of two major polypeptides with molecular weights of 23 and 13 kD and a minor polypeptide with a molecular weight of 19 kDa, which specifically reacted with the antibodies to the 30-membered peptide of the central part of the NSP protein of influenza A virus. Thus, the genomic-polarity RNA of segment 8 of influenza virus A has a translational template function. These data provide further confirmation of the concept of the bipolar (ambisens) strategy of functioning of the influenza A virus genome.

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The change in the phenotypic properties resulting from amino acid substitutions in the hemagglutinin (HA) molecule is an important link in the evolutionary process of influenza viruses. It is believed to be one of the mechanisms of the emergence of highly pathogenic strains of influenza A viruses, including subtype H5N1. Using the site-directed mutagenesis, we introduced mutations in the HA gene of the H5N1 subtype of influenza A virus.

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Aims: A portable bioaerosol monitor is greatly demanded technology in many areas including air quality control, occupational exposure assessment and health risk evaluation, environmental studies and, especially, in defence and bio-terrorism applications. Our recent groundwork allowed us to formulate the concept of a portable bioaerosol monitor, which needs to be light, user friendly, reliable and capable of detecting airborne pathogens within 1-1·5 h on the spot.

Methods And Results: Conceptually, the event of a bioaerosol concentration burst is determined by triggers to commence the representative air sampling with sequential real-time polymerase chain reaction (PCR) confirmation of the targeted micro-organism present in the air.

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Aims: In the area of bioaerosol research, rapid methods for precise detection attracted much interest over last decades. One of such technologies operating in nearly real-time mode without any specific labelling is known as surface plasmon resonance (SPR). Recently, we validated a SPR protocol in conjunction with our earlier developed personal bioaerosol sampler for rapid detection of airborne viruses.

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Clinical, histological and immunohystochemical studies of keratocystic tumors were performed showing differences in proliferative activity and MMP-9 expression scores in orthokeratinized and parakeratinised cysts. These histological features are associated with clinical course and may be used as markers for recurrence probability.

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Clinical, histological and immunohystochemical studies of ameloblastomas were performed and tumor varieties according to proliferative activity and MMP-9 expression scores were identified. These histological features are associated with clinical course and may be used as markers for recurrence probability.

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Aims: Rapid and precise bioaerosol detection in different environments has become an important research and technological issue over last decades. Previously, we employed a real-time PCR protocol in conjunction with personal bioaerosol sampler for rapid detection of airborne viruses. The approach has been proved to be specific and sensitive.

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Ameloblastoma and ameloblastic fibroma are benign odontogenous tumors of the jaws with local destructive growth, prone to recurrence. They have various typical radiological and histological features. Surgical tactic generally includes partial resection of the affected jaw.

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Bioaerosols could cause various severe human and animal diseases and their opportune and qualitative precise detection and control is becoming a significant scientific and technological topic for consideration. Over the last few decades bioaerosol detection has become an important bio-defense related issue. Many types of portable and stationary bioaerosol samplers have been developed and, in some cases, integrated into automated detection systems utilizing various microbiological techniques for analysis of collected microbes.

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Recently, we reported the outcomes of feasibility studies of a technological approach allowing rapid detection of a wide range of bioaerosols by combining a personal bioaerosol sampler with a real-time PCR technology. The protocol was found suitable for detection of targeted microorganisms within relatively short time periods. Considering the crucial importance of the PCR procedure quality control, the current paper reports the results of the development of an internally controlled PCR system for utilization by the above technology.

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Isolates of Newcastle disease virus (NDV) from deceased wild and domestic pigeons in Kazakhstan were obtained from the Almaty region during 2005 and were genotypically analyzed by using reverse transcription polymerase chain reaction (RT-PCR) with primers specific to the viral fusion (F) protein gene. Part of the amplified F protein DNA product (nucleotide sequence 47-422) and the deduced amino acid sequences were compared phylogenetically with those from strains previously reported in other geographic regions. Phylogenetic analysis indicated that the Kazakhstanian pigeon paramyxovirus type 1 (PPMV-1) isolates belong to genotype VI or 4bii.

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The F gene fragment of 79 Newcastle disease virus (NDV) strains isolated from domestic and synanthropic birds in Kazakhstan, Kirghizia, Ukraine, and Russia in 1993 to 2007 was comparatively analyzed. Phylogenetic analysis of test isolates and reference NDV strains obtained from the GenBank was carried out by polymerase chain reaction with subsequent sequencing and comparative analysis of 154-bp nucleotide sequences in the main functional region of the F gene. All newly characterized isolates belong to three NDV genotype VII subgroups: VIIa, VIIb, VIId.

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