[Intrathecal chemotherapy for leptomeningeal metastases in patients with breast cancer]. / Intratekal'naya khimioterapiya pri leptomeningeal'nom metastazirovanii u bol'nykh rakom molochnoi zhelezy.

Leptomeningeal metastases are lesions of brain and/or spinal cord sheaths by tumor cells. They occur in 5% of patients with solid tumors, although autopsies reveal these lesions much more often (10-20% of cases). Leptomengeal metastases are an unfavorable prognostic factor. Despite the modern NCCN treatment standards, including intrathecal therapy (ITT), such patients receive only irradiation of the entire brain and/or spinal cord in most cases. OBJECTIVE: To evaluate the effectiveness of ITT in patients with leptomeningeal metastases in breast cancer. MATERIAL AND METHODS: Twenty-five patients with breast cancer and leptomeningeal metastases underwent intrathecal administration of methotrexate between 2016 and 2022. Intrathecal chemotherapy was administered through lumbar puncture. We performed an intensive course (intrathecal methotrexate 15 mg 2 times a week for 1 month (8 injections), then intrathecal methotrexate 15 mg 1 time a week (4 injections), and then 15 mg 1 time a month until progression or unacceptable toxicity). RESULTS: The median duration of ITT was 2.5 months. Complete neurological responses were observed in 3 out of 25 (12%) patients, partial neurological response - in 15 out of 25 (60%) patients, progression of neurological symptoms - in 7 (28%) patients. The number of complete cytological responses was observed in 6 out of 25 (24%) patients. The median overall survival after ITT was 6.7 months. CONCLUSION: Effectiveness of ITT is confirmed by higher quality of life (72% of patients), complete cytological responses (24%) and improvement in neuroimaging data. This is an important criterion for severe patients with limited treatment options. First-stage ITT before whole-brain irradiation is preferable, as this approach increases overall survival by 3 months. Undoubtedly, ITT is a treatment option that can be used in routine clinical practice for lesions of brain and spinal cord sheaths.

[Modern possibilities of neurosurgical treatment of brain metastases]. / Sovremennye vozmozhnosti neirokhirurgicheskogo lecheniya patsientov s metastaticheskim porazheniem golovnogo mozga.

Despite significant progress in neuroimaging and introduction of new combined treatments for solid tumors, brain metastases are still adverse factor for overall survival. Brain metastases are diagnosed in 8-10% of patients and associated with extremely poor prognosis. These lesions result focal and general cerebral symptoms. Literature review highlights the current principles of surgical treatment of metastatic brain lesions in patients with solid tumors.

Pump-probe localization technique of varying solid contacts.

A baseline-free defect localization method in thin plates is proposed and tested. In this proof-of-concept work, a steel ball pressed against an aluminum plate is used to mimic a surface contact defect. The technique takes benefit of a repetitive nonlinear pump-probe interaction with a backpropagation imaging algorithm. High-frequency probe waves are periodically emitted by a piezoelectric patch transducer glued to the plate. Propagated flexural waves are recorded using a distributed array of transducers. At the same time, a continuous low-frequency pump vibration provided by a shaker fixed to the plate modulates the contact state. By combining multiple probe signals, the contact can be successfully localized. Contrast of the localization images is finally improved by a factor of 3 to 5 by implementing a modified version based on synchronous detection of the imaging algorithm.

Regulation of Thiamine (Vitamin B1)-Dependent Metabolism in Mammals by p53.

Transcriptional factor p53 is a master regulator of energy metabolism. Energy metabolism strongly depends on thiamine (vitamin B1) and/or its natural derivatives. Thiamine diphosphate (ThDP), which is a major thiamine derivative, affects p53 binding to DNA. In order to elucidate the mechanism of regulation of thiamine-dependent metabolism by p53, we assessed putative p53-binding sites near transcription starting points in genes coding for transporters and enzymes, whose function is associated with thiamine and/or its derivatives. The predictions were validated by studying cell metabolic response to the p53 inducer cisplatin. Expression of p53 and its known target, p21, has been evaluated in cisplatin-treated and control human lung adenocarcinoma A549 cells that possess functional p53 pathway. We also investigated the activity of enzymes involved in the thiamine-dependent energy metabolism. Along with upregulating the expression of p53 and p21, cisplatin affected the activities of metabolic enzymes, whose genes were predicted as carrying the p53-binding sites. The activity of glutamate dehydrogenase GDH2 isoenzyme strongly decreased, while the activities of NADP+-dependent isocitrate dehydrogenase (IDH) and malic enzymes, as well as the activity of 2-oxoglutarate dehydrogenase complex at its endogenous ThDP level, were elevated. Simultaneously, the activities of NAD+-dependent IDH, mitochondrial aspartate aminotransferase, and two malate dehydrogenase isoenzymes, whose genes were not predicted to have the p53-binding sequences near the transcription starting points, were upregulated by cisplatin. The p53-dependent regulation of the assayed metabolic enzymes correlated with induction of p21 by p53 rather than induction of p53 itself.

Local damage detection by nonlinear coda wave interferometry combined with time reversal.

Coda wave interferometry (CWI) is a sensitive ultrasound method for the detection of weak and local changes in complex inhomogeneous media. In a nonlinear modification of the method discussed here, a high-frequency probe coda is compared to its replica obtained in the presence of low-frequency pumping. If, after the filtering-out of low frequencies, the coda signals are different, this is attributed to nonlinear pump-probe interaction induced by contact acoustical nonlinearity in the damaged zone. Actually, the CWI methods are used for global inspection of complex media, such as for example, concrete structures. In this work, a step forward is made; it consists in combining the CWI with the time-reversal (TR) technique in order to allow one to focus the pump wave on a selected area in the structure and to detect and localize a flaw. Time-reverse pump is possible only in pulsed mode due to the spatio-temporal wave compression. By this reason, the particularities of coda wave mixing in conventionally used continuous and pulsed pump mode are considered. It has been experimentally observed that an aftereffect of a pulsed pump provides a nonlinear interaction between pump and probe waves of a sufficient overall level for defect detection with TR. Finally, it was shown that a TR focusing even with the minimal available quality i.e., with only one transducer produces a sufficient contrast allowing to distinguish intact and damaged zones with nonlinear CWI.

Thiamine Mono- and Diphosphate Phosphatases in Bovine Brain Synaptosomes.

Neurodegenerative diseases are accompanied by changes in the activity of thiamine mono- and diphosphate phosphatases, but molecular identification of these mammalian enzymes is incomplete. In this work, the protein fraction of bovine brain synaptosomes displaying phosphatase activity toward thiamine derivatives was subjected to affinity chromatography on thiamine-Sepharose. Protein fractions eluted with thiamine (pH 7.4 or 5.6), NaCl, and urea were assayed for the phosphatase activity against thiamine monophosphate (ThMP), thiamine diphosphate (ThDP), and structurally similar purine nucleotides. Proteins in each fraction were identified by mass spectrometry using the SwissProt database for all organisms because of insufficient annotation of the bovine genome. Peptides of two annotated bacterial phosphatases, alkaline phosphatase L from the DING protein family and exopolyphosphatase, were identified in the acidic thiamine eluate. The abundance of peptides of alkaline phosphatase L and exopolyphosphatase in the eluted fractions correlated with ThMPase and ThDPase activities, respectively. The elution profiles of the ThMPase and ThDPase activities differed from the elution profiles of nucleotide phosphatases, thus indicating the specificity of these enzymes toward thiamine derivatives. The search for mammalian DING phosphatases in the eluates from thiamine-Sepharose revealed X-DING-CD4, mostly eluted by the acidic thiamine solution (pH 5.6). The identified exopolyphosphatase demonstrated structural similarity with apyrases possessing the ThDPase activity. The obtained results demonstrate that mammalian DING proteins and apyrases exhibit ThMPase and ThDPase activity, respectively.

Regulation of Malate Dehydrogenases and Glutamate Dehydrogenase of Mammalian Brain by Thiamine in vitro and in vivo.

To study the mechanisms of the non-coenzyme action of thiamine and its diphosphate (ThDP) on brain proteins, proteins of acetone extract of bovine brain synaptosomes or the homogenate of rat brain cortex were subjected to affinity chromatography on thiamine-modified Sepharose. In the step-wise eluates by thiamine (at pH 7.4 or 5.6), NaCl, and urea, the occurrence of glutamate dehydrogenase (GDH) and isoenzymes of malate dehydrogenase (MDH) along with the influence of thiamine and/or ThDP on the enzymatic activities were characterized using mass spectrometry and kinetic experiments. Maximal activation of the malate dehydrogenase reaction by thiamine is observed after the protein elution with the acidic thiamine solution, which does not elute the MDH1 isoenzyme. Effects of exogenous thiamine or ThDP on the GDH activity may depend on endogenous enzyme regulators. For example, thiamine and/or ThDP activate the brain GDH in eluates from thiamine-Sepharose but inhibit the enzyme in the crude preparations applied to the sorbent. Inhibition of GDH by ThDP is observed using the ADP-activated enzyme. Compared to the affinity chromatography employing the elution by thiamine at pH 7.4, the procedure at pH 5.6 decreases the activation of GDH by thiamine (but not ThDP) in the eluates with NaCl and urea. Simultaneously, the MDH2 content and total GDH activity are higher after the affinity elution at pH 5.6 than at pH 7.4, suggesting the role of the known interaction of GDH with MDH2 in stabilizing the activity of GDH and in the regulation of GDH by thiamine. The biological potential of thiamine-dependent regulation of the brain GDH is confirmed in vivo by demonstration of changes in regulatory properties of GDH after administration of a high dose of thiamine to rats. Bioinformatics analysis of the thiamine-eluted brain proteins shows a specific enrichment of their annotation terms with "phosphoprotein", "acetylation", and "methylation". The relationship between thiamine and the posttranslational modifications in brain may contribute to the neuroprotective effects of high doses of thiamine, including the regulation of oxidation of the major excitatory neurotransmitter in brain - glutamate.

Mechanisms of Non-coenzyme Action of Thiamine: Protein Targets and Medical Significance.

Thiamine (vitamin B1) is a precursor of the well-known coenzyme of central metabolic pathways thiamine diphosphate (ThDP). Highly intense glucose oxidation in the brain requires ThDP-dependent enzymes, which determines the critical significance of thiamine for neuronal functions. However, thiamine can also act through the non-coenzyme mechanisms. The well-known facilitation of acetylcholinergic neurotransmission upon the thiamine and acetylcholine co-release into the synaptic cleft has been supported by the discovery of thiamine triphosphate (ThTP)-dependent phosphorylation of the acetylcholine receptor-associated protein rapsyn, and thiamine interaction with the TAS2R1 receptor, resulting in the activation of synaptic ion currents. The non-coenzyme regulatory binding of thiamine compounds has been demonstrated for the transcriptional regulator p53, poly(ADP-ribose) polymerase, prion protein PRNP, and a number of key metabolic enzymes that do not use ThDP as a coenzyme. The accumulated data indicate that the molecular mechanisms of the neurotropic action of thiamine are far broader than it has been originally believed, and closely linked to the metabolism of thiamine and its derivatives in animals. The significance of this topic has been illustrated by the recently established competition between thiamine and the antidiabetic drug metformin for common transporters, which can be the reason for the thiamine deficiency underlying metformin side effects. Here, we also discuss the medical implications of the research on thiamine, including the role of thiaminases in thiamine reutilization and biosynthesis of thiamine antagonists; molecular mechanisms of action of natural and synthetic thiamine antagonists, and biotransformation of pharmacological forms of thiamine. Given the wide medical application of thiamine and its synthetic forms, these aspects are of high importance for medicine and pharmacology, including the therapy of neurodegenerative diseases.

Thiamine Induces Long-Term Changes in Amino Acid Profiles and Activities of 2-Oxoglutarate and 2-Oxoadipate Dehydrogenases in Rat Brain.

Molecular mechanisms of long-term changes in brain metabolism after thiamine administration (single i.p. injection, 400 mg/kg) were investigated. Protocols for discrimination of the activities of the thiamine diphosphate (ThDP)-dependent 2-oxoglutarate and 2-oxoadipate dehydrogenases were developed to characterize specific regulation of the multienzyme complexes of the 2-oxoglutarate (OGDHC) and 2-oxoadipate (OADHC) dehydrogenases by thiamine. The thiamine-induced changes depended on the brain-region-specific expression of the ThDP-dependent dehydrogenases. In the cerebral cortex, the original levels of OGDHC and OADHC were relatively high and not increased by thiamine, whereas in the cerebellum thiamine upregulated the OGDHC and OADHC activities, whose original levels were relatively low. The effects of thiamine on each of the complexes were different and associated with metabolic rearrangements, which included (i) the brain-region-specific alterations of glutamine synthase and/or glutamate dehydrogenase and NADP+-dependent malic enzyme, (ii) the brain-region-specific changes of the amino acid profiles, and (iii) decreased levels of a number of amino acids in blood plasma. Along with the assays of enzymatic activities and average levels of amino acids in the blood and brain, the thiamine-induced metabolic rearrangements were assessed by analysis of correlations between the levels of amino acids. The set and parameters of the correlations were tissue-specific, and their responses to the thiamine treatment provided additional information on metabolic changes, compared to that gained from the average levels of amino acids. Taken together, the data suggest that thiamine decreases catabolism of amino acids by means of a complex and long-term regulation of metabolic flux through the tricarboxylic acid cycle, which includes coupled changes in activities of the ThDP-dependent dehydrogenases of 2-oxoglutarate and 2-oxoadipate and adjacent enzymes.

Primary Structure of 28S rRNA Gene Confirms Monophyly of Free-Living Heterotrophic and Phototrophic Apicomplexans (Alveolata).

Phylogenetic analysis of large subunit ribosomal RNA (LSU rRNA or 28S rRNA) gene sequences from free-living predatory flagellates Colpodella angusta, Voromonas pontica, and Alphamonas edax (Apicomplexa) confirms their close relationship with chromerids Chromera velia and Vitrella brassicaformis, which possess a functional photosynthetic plastid. Together these organisms form a sister group to parasitic apicomplexans (coccidians and gregarines, or sporozoans sensu lato). This result agrees with the previous conclusion on monophyly of colpodellids and chromerids (chrompodellids) based on phylogenomic data. The revealed relationships demonstrate a complex pattern of acquisition, loss, or modification of plastids and transition to parasitism during alveolate evolution.

Phylogenetic analysis of entomoparasitic nematodes, potential control agents of flea populations in natural foci of plague.

Entomoparasitic nematodes are natural control agents for many insect pests, including fleas that transmit Yersinia pestis, a causative agent of plague, in the natural foci of this extremely dangerous zoonosis. We examined the flea samples from the Volga-Ural natural focus of plague for their infestation with nematodes. Among the six flea species feeding on different rodent hosts (Citellus pygmaeus, Microtus socialis, and Allactaga major), the rate of infestation varied from 0 to 21%. The propagation rate of parasitic nematodes in the haemocoel of infected fleas was very high; in some cases, we observed up to 1,000 juveniles per flea specimen. Our study of morphology, life cycle, and rDNA sequences of these parasites revealed that they belong to three distinct species differing in the host specificity. On SSU and LSU rRNA phylogenies, these species representing three genera (Rubzovinema, Psyllotylenchus, and Spilotylenchus), constitute a monophyletic group close to Allantonema and Parasitylenchus, the type genera of the families Allantonematidae and Parasitylenchidae (Nematoda: Tylenchida). We discuss the SSU-ITS1-5.8S-LSU rDNA phylogeny of the Tylenchida with a special emphasis on the suborder Hexatylina.

[On the phylogenetic position of Hexapoda within the Pancrustacea].

Contemporary views on the phylogeny of arthropods are at odds with the traditional system, which recognizes four independent arthropod classes: Chelicerata, Crustacea, Myriapoda and Insecta. There is compelling evidence that insects in fact comprise a monophyletic lineage with Crustacea within a larger clade of Pancrustacea (=Tetraconata). Which crustacean group is the closest living relative of insects remains an open question. Recent phylogenetic analyses based on multiple genes suggest their sistership with "lower" crustaceans, the Branchiopoda. This relationship was often impeached to be caused by the long branch attraction artifact. We analyzed concatenated data on 77 ribosomal proteins, elongation factor 1 alpha (EF1A), initiation factor 5 alpha (alF5A) and other selected nuclear and mitochondrial proteins. Nuclear protein data supports the monophyly of Hexapoda, the clade uniting entognath and ectognath insects. Hexapoda and Branchiopoda comprise a monophyletic lineage in most analyses. Maxillopoda occupies the sister position to the Hexapoda + Branchiopoda. "Higher" crustaceans, the Malacostraca, in most reconstructions comprise a more basal lineage withinthe Pancrustacea. Molecular synapomorphies in low homoplastic regions are found for the clades Hexapoda Branchiopoda + Maxillopoda and the monophyletic Malacostraca containing the Phyllocarida. Therefore, the sistership of Hexapoda and Branchiopoda and their position within Entomostraca may in fact represent bona fide phylogenetic relationships.

Modeling of acoustic penetration into sandy sediments: physical and geometrical aspects.

Two different approaches to the problem of acoustic penetration into sandy marine sediments are considered: application of the Buckingham constitutive model for sediment with a plane surface and boundary element analysis of a rough surface of sediment represented as a homogeneous fluid. By a careful modeling of the constitutive behavior for plane seafloors, it is possible to partly reproduce some features of known experimental dependencies for acoustical pressure. However, accounting for roughness appears to be more important. Accordingly, the authors present a detailed numerical analysis of penetration into rough sediments using the boundary element method. The simulation results support conclusions reached by other investigators and demonstrate how local surface irregularities violate the evanescence condition that holds for a plane interface at subcritical incidence, thus considerably increasing penetration. The results apply to the frequency range 0.5-50 kHz and grazing angles larger than approximately 6 degrees -8 degrees at 10-50 kHz. For lower frequencies, when diffraction becomes important, the lowest possible grazing angle strongly depends on the range covered by the incident beam and is, in general, considerably larger. The authors provide several characteristic examples with frequencies 5 and 15 kHz and grazing angles 15 degrees -30 degrees illustrating the impact of roughness on penetration.

Acoustic probing of the jamming transition in an unconsolidated granular medium.

Experimentally determined dispersion relations for acoustic waves guided along the mechanically free surface of an unconsolidated granular packed structure provide information on the elasticity of granular media at very low pressures that are naturally controlled by the gravitational acceleration and the depth beneath the surface. The experiments confirm recent theoretical predictions that relaxation of the disordered granular packing through nonaffine motion leads to a peculiar scaling of shear rigidity with pressure near the jamming transition corresponding to zero pressure.

[Molecular phylogeny of gastrotricha based on 18S rRNA genes comparison: rejection of hypothesis of relatedness with nematodes].

Gastrotrichs are meiobenthic free-living aquatic worms whose phylogenetic and intra-group relationships remain unclear despite some attempts to resolve them on the base of morphology or molecules. In this study we analysed complete sequences of the 18S rRNA gene of 15 taxa (8 new and 7 published) to test numerous hypotheses on gastrotrich phylogeny and to verify whether controversial interrelationships from previous molecular data could be due to the short region available for analysis and the poor taxa sampling. Data were analysed using both maximum likelihood and Bayesian inference. Results obtained suggest that gastrotrichs, together with Gnathostomulida, Plathelminthes, Syndermata (Rotifera + Acanthocephala), Nemertea and Lophotrochozoa, comprise a clade Spiralia. Statistical tests reject phylogenetic hypotheses regarding Gastrotricha as close relatives of Nematoda and other Ecdysozoa or placing them at the base of bilaterian tree close to acoels and nemertodermatides. Within Gastrotricha, Chaetonotida and Macrodasyida comprise two well supported clades. Our analysis confirmed the monophyly of the Chaetonotidae and Xenotrichulidae within Chaetonida as well as Turbanellidae and Thaumastodermatidae within Macrodasyida. Mesodasys is a sister group of the Turbanellidae, and Lepidodasyidae appears to be a polyphyletic group as Cephalodasys forms a separate lineage at the base of macrodasyids, whereas Lepidodasys groups with Neodasys between Thaumastodermatidae and Turbanellidae. To infer a more reliable Gastrotricha phylogeny many species and additional genes should be involved in future analyses.

Acoustic modes propagating along the free surface of granular media.

In unconsolidated granular materials under gravity there exist acoustical waves propagating along the surface with anomalously low sound velocity. The presented theory describes these guided surface acoustic modes (GSAM) confined between the surface of the granular materials and in-depth layers with increasing rigidity. The analysis is based on the obtained original analytical solution of the Helmholtz equation that has never been used both in classical and quantum mechanics. This solution is valid for a particular rigidity profile, whereas the general case of grains with or without adhesion has been analyzed numerically. In contrast to the Rayleigh wave polarized in the sagittal (vertical) plane, which is the unique localized mode in a homogeneous solid, an infinite number of modes with sagittal polarization as well as an infinite number of shear horizontal modes have been found. The difference in physical mechanisms of localization is discussed, and the transformation of the GSAMs into the Rayleigh wave at the increasing adhesion is demonstrated: The first sagittal mode transforms into the Rayleigh one, while the others delocalize. The theory explains the experimentally observed magnitude of velocity for the acoustic waves in sand elliptically polarized in the sagittal plane.

Do we need many genes for phylogenetic inference?

Fifty-six nuclear protein coding genes from Taxonomically Broad EST Database and other databases were selected for phylogenomic-based examination of alternative phylogenetic hypotheses concerning intergroup relationship between multicellular animals (Metazoa) and other representatives of Opisthokonta. The results of this work support sister group relationship between Metazoa and Choanoflagellata. Both of these groups form the taxon Holozoa along with the monophyletic Ichthyosporea or Mesomycetozoea (a group that includes Amoebidium parasiticum, Sphaeroforma arctica, and Capsaspora owczarzaki). These phylogenetic hypotheses receive high statistical support both when utilizing whole alignment and when only 5000 randomly selected alignment positions are used. The presented results suggest subdivision of Fungi into Eumycota and lower fungi, Chytridiomycota. The latter form a monophyletic group that comprises Chytridiales+Spizellomycetales+Blastocladiales (Batrachochytrium, Spizellomyces, Allomyces, Blastocladiella), contrary to the earlier reports based on the analysis of 18S rRNA and a limited set of protein coding genes. The phylogenetic distribution of genes coding for a ubiquitin-fused ribosomal protein S30 implies at least three independent cases of gene fusion: in the ancestors of Holozoa, in heterotrophic Heterokonta (Oomycetes and Blastocystis) and in the ancestors of Cryptophyta and Glaucophyta. Ubiquitin-like sequences fused with ribosomal protein S30 outside of Holozoa are not FUBI orthologs. Two independent events of FUBI replacement by the ubiquitin sequence were detected in the lineage of C. owczarzaki and in the monophyletic group of nematode worms Tylenchomorpha+Cephalobidae. Bursaphelenchus xylophilus (Aphelenchoidoidea) retains a state typical of the rest of the Metazoa. The data emphasize the fact that the reliability of phylogenetic reconstructions depends on the number of analyzed genes to a lesser extent than on our ability to recognize reconstruction artifacts.

[Export of metabolites by the proteins of the DMT and RhtB families and its possible role in intercellular communication].

The earlier published and new experimental data are summarized on the properties of the genes encoding the membrane proteins of the DMT family (RhtA (YbiF), EamA (YdeD), YijE, YddG, YedA, PecM, eukaryotic nucleoside phosphate sugar and hexose phosphate transporters), the RhtB/LysE family (RhtB, RhtC, LeuE, YahN, EamB (YfiK), ArgO (YggA), CmaU), as well as some other families (YicM, YdhC, YdeAB, YdhE (NorE)). These proteins are involved in the export of amino acids, purines, and other metabolites from the cell. The expression of most of the genes encoding these proteins is not induced by the substrates they transport but is controlled by the global regulation systems, such as the Lrp protein, and activated by the signal compounds involved in the intracellular communication. The level of expression, assessed in experiments on translational fusion of the corresponding bacterial genes with the beta-galactosidase gene, depends on the growth phase of the bacterial culture, composition of the medium, and some stress factors, such as pH osmolarity or decreased aeration. The efflux of normal cell metabolites is assumed to be the natural function of these proteins. This function may play a role in density-dependent behavior of cell populations (quorum sensing). It may have been enhanced in the course of evolution via specialization of these proteins in the efflux of compounds derived from metabolic intermediates and adjusted to the role of transmitters.

Acoustic waves in an elastic channel near the free surface of granular media.

A theoretical description of a natural acoustical waveguide existing in unconsolidated granular materials due to a gravity-induced stiffness gradient is proposed. The analytical theory for the acoustic modes propagating in the medium with a power-law type inhomogeneity uses some original solutions of the Helmholtz equation that have not been derived before either in classical or in quantum mechanics. The dispersion relations and a physical mechanism of localization for these modes indicate their essential difference both from the Rayleigh surface acoustic waves and the waveguide modes in homogeneous plates.

[Characterization of enterobacteria producing the low-molecular-weight antibiotics microcins]. / Kharakteristika énterobakterii, produtsiruiushchikh mikrotsiny--nizkomolekuliarnye antibiotiki.

A comparative study of the morphological, cultural, physiological, and biochemical properties of the microcinogenic strains EcS 5/98, EcS 6/98, and EcB 214/99 with the known microcin C51 producer Escherichia coli M17(p74) showed that these strains belong to the species E. coli. The strains produced microcins with molecular masses lower than 10 kDa. Microcin biosynthesis was stimulated by a deficiency of nutrients in the cultivation media. Microcins were found to be resistant to thermolysin, but were degraded by pronase, protolichetrem, and the Bacillus mesentericus metalloproteinase. This indicated that microcins are peptides or contain peptides in their molecules. The study of cross immunity to microcins and the sequence of their genetic determinants showed that the microcins of strains EcS 5/98 and EcS 6/98 are of B type, whereas the microcin of strain EcB 214/99 presumably belongs to another type, since it suppresses the growth of the producers of C-type and B-type microcins. The new microcin producers possess antibacterial activity against natural isolates belonging to the genera Escherichia and Salmonella, against a wide range of colicinogenic Escherichia strains, and against the collection Salmonella cultures.