Phage therapy is now seen as a promising way to overcome the current global crisis in the spread of multidrug-resistant bacteria. However, phages are highly strain-specific, and in most cases one ...will have to isolate a new phage or search for a phage suitable for a therapeutic application in existing libraries. At an early stage of the isolation process, rapid screening techniques are needed to identify and type potential virulent phages. Here, we propose a simple PCR approach to differentiate between two families of virulent Staphylococcus phages (Herelleviridae and Rountreeviridae) and eleven genera of virulent Klebsiella phages (Przondovirus, Taipeivirus, Drulisvirus, Webervirus, Jiaodavirus, Sugarlandvirus, Slopekvirus, Jedunavirus, Marfavirus, Mydovirus and Yonseivirus). This assay includes a thorough search of a dataset comprising S. aureus (n = 269) and K. pneumoniae (n = 480) phage genomes available in the NCBI RefSeq/GenBank database for specific genes that are highly conserved at the taxonomic group level. The selected primers showed high sensitivity and specificity for both isolated DNA and crude phage lysates, which permits circumventing DNA purification protocols. Our approach can be extended and applied to any group of phages, given the large number of available genomes in the databases.
The chemical investigation of marine mollusks has led to the isolation of a wide variety of bioactive metabolites, which evolved in marine organisms as favorable adaptations to survive in different ...environments. Most of them are derived from food sources, but they can be also biosynthesized de novo by the mollusks themselves, or produced by symbionts. Consequently, the isolated compounds cannot be strictly considered as “chemotaxonomic markers” for the different molluscan species. However, the chemical investigation of this phylum has provided many compounds of interest as potential anticancer drugs that assume particular importance in the light of the growing literature on cancer biology and chemotherapy. The current review highlights the diversity of chemical structures, mechanisms of action, and, most importantly, the potential of mollusk‐derived metabolites as anticancer agents, including those biosynthesized by mollusks and those of dietary origin. After the discussion of dolastatins and kahalalides, compounds previously studied in clinical trials, the review covers potentially promising anticancer agents, which are grouped based on their structural type and include terpenes, steroids, peptides, polyketides and nitrogen‐containing compounds. The “promise” of a mollusk‐derived natural product as an anticancer agent is evaluated on the basis of its ability to target biological characteristics of cancer cells responsible for poor treatment outcomes. These characteristics include high antiproliferative potency against cancer cells in vitro, preferential inhibition of the proliferation of cancer cells over normal ones, mechanism of action via nonapoptotic signaling pathways, circumvention of multidrug resistance phenotype, and high activity in vivo, among others. The review also includes sections on the targeted delivery of mollusk‐derived anticancer agents and solutions to their procurement in quantity.
The Twort-like myoviruses (
genus) of
are promising agents for bacteriophage therapy due to a broad host range and high killing activity against clinical isolates. This work improves the current ...understanding of the phage infection physiology by transcriptome analysis. The expression profiles of a typical member of the
genus (vB_SauM-515A1) were obtained at three time-points post-infection using RNA sequencing. A total of 35 transcription units comprising 238 ORFs were established. The sequences for 58 early and 12 late promoters were identified in the phage genome. The early promoters represent the strong sigma-70 promoters consensus sequence and control the host-dependent expression of 26 transcription units (81% of genes). The late promoters exclusively controlled the expression of four transcription units, while the transcription of the other five units was directed by both types of promoters. The characteristic features of late promoters were long -10 box of TGTTATATTA consensus sequence and the absence of -35 boxes. The data obtained are also of general interest, demonstrating a strategy of the phage genome expression with a broad overlap of the early and late transcription phases without any middle transcription, which is unusual for the large phage genomes (>100 kbp).
This study provides insights into the flexibility of the mitochondrial genome in sunflower (
L.) as well as into the causes of ANN2-type cytoplasmic male sterility (CMS).
assembly of the ...mitochondrial genome of male-sterile HA89(ANN2) sunflower line was performed using high-throughput sequencing technologies. Analysis of CMS ANN2 mitochondrial DNA sequence revealed the following reorganization events: twelve rearrangements, seven insertions, and nine deletions. Comparisons of coding sequences from the male-sterile line with the male-fertile line identified a deletion of
and seven new transcriptionally active open reading frames (ORFs):
,
,
,
,
,
,
. Three of these ORFs represent chimeric genes involving
(
),
(
), and
(
). In addition,
,
,
, as well as
, encode proteins containing membrane domain(s), making them the most likely candidate genes for CMS development in ANN2. Although the investigated CMS phenotype may be caused by simultaneous action of several candidate genes, we assume that
plays a major role in developing male sterility in ANN2. Comparative analysis of mitogenome organization in sunflower lines representing different CMS sources also allowed identification of reorganization hot spots in the mitochondrial genome of sunflower.
Bacteriophage therapy is considered one of the most promising therapeutic approaches against multi-drug resistant bacterial infections. Infections caused by Staphylococcus aureus are very efficiently ...controlled with therapeutic bacteriophage cocktails, containing a number of individual phages infecting a majority of known pathogenic S. aureus strains. We assessed the contribution of individual bacteriophages comprising a therapeutic bacteriophage cocktail against S. aureus in order to optimize its composition. Two lytic bacteriophages vB_SauM-515A1 (Myoviridae) and vB_SauP-436A (Podoviridae) were isolated from the commercial therapeutic cocktail produced by Microgen (Russia). Host ranges of the phages were established on the panel of 75 S. aureus strains. Phage vB_SauM-515A1 lysed 85.3% and vB_SauP-436A lysed 68.0% of the strains, however, vB_SauP-436A was active against four strains resistant to vB_SauM-515A1, as well as to the therapeutic cocktail per se. Suboptimal results of the therapeutic cocktail application were due to extremely low vB_SauP-436A1 content in this composition. Optimization of the phage titers led to an increase in overall cocktail efficiency. Thus, one of the effective ways to optimize the phage cocktails design was demonstrated and realized by using bacteriophages of different families and lytic spectra.
The widespread use of antimicrobials causes antibiotic resistance in bacteria. The use of butyric acid and its derivatives is an alternative tactic. This review summarizes the literature on the role ...of butyric acid in the body and provides further prospects for the clinical use of its derivatives and delivery methods to the animal body. Thus far, there is evidence confirming the vital role of butyric acid in the body and the effectiveness of its derivatives when used as animal medicines and growth stimulants. Butyric acid salts stimulate immunomodulatory activity by reducing microbial colonization of the intestine and suppressing inflammation. Extraintestinal effects occur against the background of hemoglobinopathy, hypercholesterolemia, insulin resistance, and cerebral ischemia. Butyric acid derivatives inhibit histone deacetylase. Aberrant histone deacetylase activity is associated with the development of certain types of cancer in humans. Feed additives containing butyric acid salts or tributyrin are used widely in animal husbandry. They improve the functional status of the intestine and accelerate animal growth and development. On the other hand, high concentrations of butyric acid stimulate the apoptosis of epithelial cells and disrupt the intestinal barrier function. This review highlights the biological activity and the mechanism of action of butyric acid, its salts, and esters, revealing their role in the treatment of various animal and human diseases. This paper also discussed the possibility of using butyric acid and its derivatives as surface modifiers of enterosorbents to obtain new drugs with bifunctional action.
O-GlcNAc hydrolase (OGA) catalyzes removal of βα-linked N-acetyl-D-glucosamine from serine and threonine residues. We report crystal structures of Homo sapiens OGA catalytic domain in apo and ...inhibited states, revealing a flexible dimer that displays three unique conformations and is characterized by subdomain α-helix swapping. These results identify new structural features of the substrate-binding groove adjacent to the catalytic site and open new opportunities for structural, mechanistic and drug discovery activities.
“Mixed” calcium rare-earth aluminate laser host crystals Ca(Gd,Lu)AlO4 (CALGLO) with up to 10.8 at.% Lu codoped with Tm3+ and Ho3+ ions are grown by the Czochralski method along the 001 direction. ...The segregation of rare-earth ions is studied. The crystal structure is refined by the Rietveld method. Tm,Ho:Ca(Gd,Lu)AlO4 crystallizes in the tetragonal system (sp. gr. I4/mmm) exhibiting a K2NiF4 type structure. The lattice constants are a = 3.6585(6) Å and c = 11.9660(9) Å for a crystal with a composition of CaGd0.8947Lu0.0551Tm0.0448Ho0.0054AlO4. The stability of Ca(Gd,Lu)AlO4 solid-solutions is discussed. The polarized Raman spectra are measured, revealing a most intense mode at 311 cm−1 and a maximum phonon frequency of ∼650 cm−1. The polarized absorption spectra are measured. The transition intensities for the Ho3+ ion are analyzed using the modified Judd-Ofelt theory accounting for configuration interaction.
•Tm3+,Ho3+-codoped “mixed” disordered Ca(Ga,Lu)AlO4 aluminate crystal.•Rietveld refinement of the crystal structure and discussion of the crystal disorder.•The stability of CaGd1-xLuxAlO4 solid-solutions is discussed.•Polarized Raman spectra are measured, revealing the most intense mode at 311 cm−1.•Transition intensities for Ho3+ ions are analyzed using the modified Judd-Ofelt theory.
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The sequential adsorption of phenylalanine and salicylic acid on a carbon sorbent was studied. The influence of modification conditions, including the sorbent/solution volume ratio, ...amino acid concentration, temperature and pH, on the adsorption parameters of phenylalanine, as well as the physicochemical properties of the resulting carbon sorbent sample, was established. The effect of sequential adsorption of phenylalanine and salicylic acid on the physicochemical characteristics of sorbents is shown.
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