12 research outputs found

    The effect of three complexes of iodine with amino acids on gene expression of model antibiotic resistant microorganisms Escherichia coli ATCC BAA-196 and Staphylococcus aureus ATCC BAA-39

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    DATA AVAILABILITY STATEMENT : The RNA reads generated for this study are available from the NCBI SRA database through the BioProjects PRJNA557356 and PRJNA480363 created, respectively, for the genomes of E. coli ATCC BAA-196 and S. aureus ATCC BAA-39. The links to the respective SRA Experiments are available on the BioProjectWeb-pages. The predicted X-ray structures of the complexes KS25, KS33, and KS51 were deposited at the CCDC database (https://www.ccdc.cam.ac. uk/, accessed on 26 June 2023) under accession numbers 1036607, 1036667, and 1436137, respectively.SUPPLEMENTARY INFORMATION : SUPPLEMENTARY TABLE S1. X-ray diffraction and refinement parameters; SUPPLEMENTARY TABLE S2. Genes regulated with statistical reliability (|fold change| 2.0; p-value 0.05) under the effect of iodine-containing complexes at least at one condition; SUPPLEMENTARY TABLE S3. Regulation of expression of genes involved in the central metabolism of bacteria by the three tested complexes.BACKGROUND : Iodine is a broad-spectrum antimicrobial disinfectant for topical application. Recent studies have shown promising results on the applicability of an iodine-containing complex, FS-1, against antibiotic-resistant pathogens. It was hypothesized that the antimicrobial activity of iodine-containing complexes may be modulated by the organic moiety of the complex, i.e., amino acids. METHODS : Gene regulation and metabolic alterations were studied in two model multidrug-resistant microorganisms, Staphylococcus aureus ATCC BAA-39, and Escherichia coli ATCC BAA- 196, treated with three complexes containing iodine and three different amino acids: glycine, Lalanine, and L-isoleucine. The bacterial cultures were exposed to sub-lethal concentrations of the complexes in the lagging and logarithmic growth phases. Gene regulation was studied by total RNA sequencing and differential gene expression analysis. RESULTS : The central metabolism of the treated bacteria was affected. An analysis of the regulation of genes involved in stress responses suggested the disruption of cell wall integrity, DNA damage, and oxidative stress in the treated bacteria. CONCLUSIONS : Previous studies showed that the application of iodine-containing complexes, such as FS-1, serves as a supplement to common antibiotics and can be a promising way to combat antibiotic-resistant pathogens. Current results shed light on possible mechanisms of this action by disrupting the cell wall barriers and imposing oxidative stress. It was also found that the effect of the complexes on metabolic pathways varied in the tested microorganisms depending on the organic moiety of the complexes and the growth phase when the complexes had been applied.The Ministry of Industry and Infrastructural Development of the Republic of Kazakhstan and the National Research Foundation (NRF) of South Africa.https://www.mdpi.com/journal/microorganismsam2024BiochemistryGeneticsMicrobiology and Plant PathologySDG-03:Good heatlh and well-bein

    The adaptive potential of North American subtype H7N2 avian influenza viruses to mammals

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    Introduction. H7 subtype avian influenza viruses causing severe epizootics among birds are phylogenetically different in the Eastern and Western hemispheres. Numerous human infections caused by these viruses in the Eastern hemisphere indicate that H7 viruses can overcome the interspecies barrier and pose a potential threat of a new pandemic.The H7N2 viruses with deletion of amino acids 221–228 (H3 numbering) in hemagglutinin (HA) had been circulating among poultry in the Western Hemisphere during 1996–2006, and had once again been detected in 2016 in an animal shelter, where they caused cat diseases. The objective of this study is to elucidate the mechanism of adaptation to mammals of North American H7N2 influenza viruses with deletion in HA. Materials and methods. The A/chicken/New Jersey/294598-12/2004 (H7N2) virus was adapted to mice by the lung passages. Complete genomes of original and mouse-adapted viruses were analyzed. The receptor specificity and thermostability of viruses, HA activation pH and virulence for mice were determined. Results. The non-pathogenic H7N2 avian influenza virus became pathogenic after 10 passages in mice. Amino acid substitutions occurred in five viral proteins: one in PB2 (E627K), NA (K127N), NEP (E14Q), four in HA and six in NS1. Mutations in HA slightly changed receptor specificity but increased the pH of HA activation by 0.4 units. The NS1 protein undergone the greatest changes in the positions (N73T, S114G, K118R, G171A, F214L and G224R), where amino acid polymorphisms were observed in the original virus, but only minor amino acid variants have been preserved in the mouse adapted variant. Conclusion. The results show that H7N2 viruses have the potential to adapt to mammals. The increase in virulence is most likely due to the adaptive E627K mutation in PB2 and possibly in HA

    Assembly of complete genome sequences of negative-control and experimental strain variants of staphylococcus aureus ATCC BAA-39 selected under the effect of the drug FS-1, which induces antibiotic resistance reversion

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    Staphylococcus aureus ATCC BAA-39 is the reference organism for a multidrug-resistant Staphylococcus aureus (MRSA) strain that was used to study druginduced resistance reversion by an iodine-containing nanomolecular complex, FS-1. PacBio sequencing was performed on both the experimental and control strains, followed by genome assembly, variant calling, and DNA modification profiling.Ministry of Industry and Infrastructural Development of the Republic of Kazakhstan and South African National Research Foundation (NRF).https://mra.asm.orgpm2020BiochemistryGeneticsMicrobiology and Plant Patholog

    Transcriptomics and methylomics study on the effect of iodine-containing drug FS-1 on Escherichia coli ATCC BAA-196

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    AIM : Promising results on application of iodine-containing nano-micelles, FS-1, against antibiotic-resistant Escherichia coli was demonstrated. MATERIALS AMD METHODS : RNA sequencing for transcriptomics and the complete genome sequencing by SMRT PacBio were followed by genome assembly and methylomics. RESULTS AND CONCLUSION : FS-1-treated E. coli showed an increased susceptibility to antibiotics ampicillin and gentamicin. Cultivation with FS-1 caused gene expression alterations toward anaerobic respiration, increased anabolism and inhibition of many nutrient uptake systems. Main targets of iodine-containing particles were cell membrane structures causing oxidative, osmotic and acidic stresses. Identification of methylated nucleotides showed an altered pattern in the FS-1-treated culture. Possible role of transcriptional and epigenetic modifications in the observed increase in susceptibility to gentamicin and ampicillin were discussed.LAY ABSTRACT : New approaches of combatting drug-resistant infections are in demand as the development of new antibiotics is in a deep crisis. This study was set out to investigate molecular mechanisms of action of new iodine-containing nano-micelle drug FS-1, which potentially may improve the antibiotic therapy of drug-resistant infections. Iodine is one of the oldest antimicrobials and until now there were no reports on development of resistance to iodine. Recent studies showed promising results on application of iodine-containing nano-micelles against antibiotic-resistant pathogens as a supplement to antibiotic therapy. The mechanisms of action, however, remain unclear. The collection strain Escherichia coli ATCC BAA-196 showing an extended spectrum of resistance to ββ-lactam and aminoglycoside antibiotics was used in this study as a model organism. Antibiotic resistance patterns, whole genomes and total RNA sequences of the FS-1-treated (FS) and negative control (NC) variants of E. coli BAA-196 were obtained and analyzed. FS culture showed an increased susceptibility to antibiotics associated with profound gene expression alterations switching the bacterial metabolism to anaerobic respiration, increased anabolism, osmotic stress response and inhibition of many nutrient uptake systems. Nucleotide methylation pattern were identified in FS and NC cultures. While the numbers of methylated sites in both genomes remained similar, some peculiar alterations were observed in their distribution along chromosomal and plasmid sequences.Sequencing was funded by the program “Study of reversion of antibiotic resistance of pathogenic microorganisms” provided by the Industrial development and industrial safety committee of the Ministry of industry and infrastructural development of the Republic of Kazakhstan. Genome assembly, annotation, bioinformatics analysis and student support were funded by the South African National Research Foundation (NRF).http://www.futuremedicine.com/loi/fmbhj2022BiochemistryGeneticsMicrobiology and Plant Patholog

    Pleiotropic effects of hemagglutinin amino acid substitutions of H5 influenza escape mutants

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    AbstractIn the present study we assessed pleiotropic characteristics of the antibody-selected mutations. We examined pH optimum of fusion, temperatures of HA heat inactivation, and in vitro and in vivo replication kinetics of the previously obtained influenza H5 escape mutants. Our results showed that HA1 N142K mutation significantly lowered the pH of fusion optimum. Mutations of the escape mutants located in the HA lateral loop significantly affected H5 HA thermostability (P<0.05). HA changes at positions 131, 144, 145, and 156 and substitutions at positions 131, 142, 145, and 156 affected the replicative ability of H5 escape mutants in vitro and in vivo, respectively. Overall, a co-variation between antigenic specificity and different HA phenotypic properties has been demonstrated. We believe that the monitoring of pleiotropic effects of the HA mutations found in H5 escape mutants is essential for accurate prediction of mutants with pandemic potential

    Improving the Structural Characteristics of Heavy Concrete by Combined Disperse Reinforcement

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    The development of perspective concrete mixes capable of resisting the action of external loads is an important scientific problem in the modern construction industry. This article presents a study of the influence of steel, basalt, and polypropylene fiber materials on concrete’s strength and deformation characteristics. A combination of various types of dispersed reinforcement is considered, and by methods of mathematical planning of the experiment, regression dependences of the strength and deformation characteristics on the combination of fibers and their volume fraction are obtained. It was shown that the increase in compressive strength was 35% in fiber-reinforced concretes made using a combination of steel and basalt fiber with a volume concentration of steel fiber of 2% and basalt fiber of 2%; tensile strength in bending increased by 79%, ultimate deformations during axial compression decreased by 52%, ultimate deformation under axial tension decreased by 39%, and elastic modulus increased by 33%. Similar results were obtained for other combinations of dispersed reinforcement. The studies carried out made it possible to determine the most effective combinations of fibers of various types of fibers with each other and their optimal volume concentration

    Numerical Simulation of the Bearing Capacity of Variotropic Short Concrete Beams Reinforced with Polymer Composite Reinforcing Bars

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    One of the disadvantages of reinforced concrete is the large weight of structures due to the steel reinforcement. A way to overcome this issue and develop new types of reinforcing elements is by using polymer composite reinforcement, which can successfully compensate for the shortcomings of steel reinforcement. Additionally, a promising direction is the creation of variotropic (transversely isotropic) building elements. The purpose of this work was to numerically analyze improved short bending concrete elements with a variotropic structure reinforced with polymer composite rods and to determine the prospects for the further extension of the results obtained for long-span structures. Numerical models of beams of a transversally isotropic structure with various types of reinforcement have been developed in a spatially and physically nonlinear formulation in ANSYS software considering cracking and crashing. It is shown that, in combination with a stronger layer of the compressed zone of the beam, carbon composite reinforcement has advantages and provides a greater bearing capacity than glass or basalt composite. It has been proven that the use of the integral characteristics of concrete and the deflections of the elements are greater than those when using the differential characteristics of concrete along the height of the section (up to 5%). The zones of the initiation and propagation of cracks for different polymer composite reinforcements are determined. An assessment of the bearing capacity of the beam is given. A significant (up to 146%) increase in the forces in the reinforcing bars and a decrease in tensile stresses (up to 210&ndash;230%) were established during the physically non-linear operation of the concrete material. The effect of a clear redistribution of stresses is in favor of elements with a variotropic cross section in height

    Complete genome sequence of collection strain acinetobacter baumannii ATCC BAA-1790, used as a model to study the antibiotic resistance reversion induced by iodine-containing complexes

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    The strain Acinetobacter baumannii ATCC BAA-1790 was sequenced as a model for nosocomial multidrug-resistant infections. Long-read PacBio sequencing revealed a circular chromosome of 3,963,235 bp with two horizontally transferred genomic islands and a 67,023-bp plasmid. Multiple antibiotic resistance genes and genome methylation patterns were identified.The Industrial Development and Industrial Safety Committee of the Ministry of Industry and Infrastructural Development of the Republic of Kazakhstan, South African National Research Foundation (NRF) and the University of Pretoria.https://mra.asm.orgam2021BiochemistryGeneticsMicrobiology and Plant Patholog

    Complete genome sequence of a multidrug-resistant strain, Escherichia coli ATCC BAA-196, as a model for studying induced antibiotic resistance reversion

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    Here, we report the complete genome sequence of the multidrugresistant Escherichia coli strain ATCC BAA-196, a model organism used for studying possible antibiotic resistance reversion induced by FS-1, an iodine-containing complex. Two genomes, representing FS-1-treated and negative-control variants and composed of a chromosome and several plasmids, were assembled.The Industrial Development and Industrial Safety Committee of the Ministry of Industry and Infrastructural Development of the Republic of Kazakhstan, the South African National Research Foundation and the University of Pretoria.https://mra.asm.orgam2020BiochemistryGeneticsMicrobiology and Plant Patholog
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