A Low-Molecular-Weight Compound Derived from Human Leukocytes Determines a Bactericidal Activity of the Interferon Preparation.

The aim of this study was to characterize the structure and mode of action of antimicrobials derived from a commercial preparation of alfa-interferon. By combination of semi-preparative/analytical reversed-phase high-performance liquid chromatography, we isolated and purified a novel active substance based on carbohydrate with a complex of amino acids, which determines antimicrobial property of commercial preparation of interferon. A size-exclusion chromatography was performed and LC/ESI-MS revealed molecular masses of active substance were in the range of 180-249 Da. Edman sequencing identified phenylthiohydantoin (PTH) derivatives which consisted a set of preliminary (Asp, Glu, Gly, and Ala) and minor amino acids (Leu and Thr) at equimolar ratio. Thus, the purified active substance is a compound containing the complex of amino acids connected with carbohydrate background and called leucidin. Leucidin demonstrated antimicrobial activity against the model Escherichia coli (E. coli) K12 strain at a minimal inhibitory concentration of 20 µg mL-1. The revealed antimicrobial mechanism of action is associated with violation of the bacterial cell wall leading to a SOS response and bacterial autolysis. Despite the preliminary nature of the results, obtained data allowed us to discover the previously unknown leukocyte-derived antimicrobial molecules.

Electronic structure and charge transport in nonstoichiometric tantalum oxide.

The atomic and electronic structure of nonstoichiometric oxygen-deficient tantalum oxide TaO x<2.5 grown by ion beam sputtering deposition was studied. The TaO x film content was analyzed by x-ray photoelectron spectroscopy and by quantum-chemistry simulation. TaO x is composed of Ta2O5, metallic tantalum clusters and tantalum suboxides. A method for evaluating the stoichiometry parameter of TaO x from the comparison of experimental and theoretical photoelectron valence band spectra is proposed. The charge transport properties of TaO x were experimentally studied and the transport mechanism was quantitatively analyzed with four theoretical dielectric conductivity models. It was found that the charge transport in almost stoichiometric and nonstoichiometric tantalum oxide can be consistently described by the phonon-assisted tunneling between traps.

Electronic structure of stoichiometric and oxygen-deficient ferroelectric Hf0.5Zr0.5O2.

The electronic structure of oxygen-deficient Hf0.5Zr0.5O2 in the non-centrosymmetric orthorhombic (ferroelectric) phase was investigated by means of x-ray photoelectron spectroscopy and first-principle density functional theory calculations. It was established that a peak in the photoelectron spectra observed at an energy above the valence band top of ferroelectric Hf0.5Zr0.5O2 in ion-etched samples was due to oxygen vacancies. A method for evaluating the oxygen vacancies concentration in the material from the comparison of experimental and theoretical photoelectron spectra of the valence band is proposed. It is found that oxygen polyvacancies are not formed in ferroelectric Hf0.5Zr0.5O2: an energy-favorable spatial arrangement of several oxygen vacancies in the crystal corresponds to the configuration formed by noninteracting vacancies distant from each other. The oxygen vacancies in five charged states were simulated. The electron levels in the bandgap caused by charged oxygen vacancies indicate that any type of oxygen vacancies in ferroelectric Hf0.5Zr0.5O2 can capture both electrons and holes, i.e. can act as an amphoteric localization center for charge carriers.

[Species structure and staphylococci bioprofile characteristics--ausative agents of perinatal infectious-inflammation pathology in children of Orenburg].

AIM: Analysis of taxonomic structure and bioprofile of staphylcocci--causative agents of cutaneous and ophthalmic forms of perinatal infectious-inflammation pathology (IIP) in Orenburg neonates. MATERIALS AND METHODS: Bacteriologic study in 308 neonates with clinical signs of cutaneous and ophthalmic forms of perinatal IIP was carried out with isolation of microorganisms from lesions and their species (genus) identification by generally accepted methods. The presence of hemolytic, anti-lysozyme, activity, ability to form biofilms, resistance to antimicrobial cationic peptides of human leukocytes (intercid) and thrombocytes (trombodefensins), sensitivity to antibiotics were determined in the isolated staphylococci strains. RESULTS: Staphylococci dominated in the structure of causative agents of cutaneous and ophthalmic forms of perinatal IIP (76.2%) and among those coagulase-negative staphylococci had a priority position (82.4 ± 3.4%). Staphylococci had a distinctive pathogenic potential and frequently had antibiotic resistance. CONCLUSION: Perinatal IIP is examined as a variant of endogenous bacterial infection. The necessity of microbiologic monitoring for development of effective approaches to therapy and prophylaxis of perinatal IIP is justified.

[Effect of thrombodefensins on the course of chronic staphylococci dermatitis on in vivo model].

AIM: Evaluate therapeutic effect of thrombodefensins (TD) on the course of chronic staphylococci dermatitis (CSD) in mice. MATERIALS AND METHODS: TD was obtained from human thrombocytes. 24 CBRB-Rb(8.17)1Iem line female mice were used in the experiment, that were divided into 2 equal groups. Staphylococcus aureus strain producing exfoliative exotoxin was isolated from withers of each mouse with signs of affection. Mice of the experiment group subcutaneously around the locus of affection, received for 4 weeks daily a composition in the volume of 0.2 ml, that contains 1 g of dry lyophilized TD diluted in 10 ml of 0.9% NaCl (final concentration of the preparation--15 µg/ml). Control group animals similarly received 0.9% solution of NaCl without TD. Area and degree of the affected zone on the back was evaluated in all the mice. Statistical significance of differences in the values of parameters was determined by t-criteria. RESULTS: At the start of the experiment the average area of the affected zone in mice of both groups was 167 ± 17 mm2. From day 8 to 23 the expansion of the affection zone was observed, however in the experiment group of mice these negative tendencies were less pronounced. At the end of the experiment on day 50 the area of affection was significantly smaller (2.3 times) in the experiment group of mice compared with the control (p < 0.05). CONCLUSION: The anti-staphylococci effect of TD, demonstrated in the study, opens perspective of their clinical use in CSD therapy.

[The comparative characteristics of antibacterial properties of the peptides of the active site of GM-CSF, and substances delivered from supernatants of hematopoietic progenitor CD34+45- cells].

The antibacterial activity of synthetic peptides of the active site of GM-CSF and supernatants of CD34+45- hematopoietic progenitor cells has been investigated GM-CSF peptides and cell supernatants were found to possess pronounced antibacterial activity, at that a combination of these substances has a more pronounced activity in comparison with the single substances. Possible mechanisms of the identified effects of synthetic peptides and substances from the supernatants of CD34+5- cells are discussed.

[Role of persistence characteristics of microorganisms in pathogenesis of endogenous infections].

Definition of endogenous bacterial infections (EBI) is formulated as well as their nosological variability is demonstrated and clinical and microbiological characteristics are characterized. Universal scheme of pathogenesis of these infections with separation of key phases of their course: premorbid phase, colonization, alteration, sanation or persistence. Important role of persistence characteristics of microorganisms for the development of EBI, which provide survival of agents during contacts with humoral and cellular effectors of host's immunity, is substantiated.

[Taxonomic spectrum and antibiotic resistance of Enterobacteriaceae isolated from bile of patients with cholangitis].

The data on the taxonomic structure and antibiotic resistance of Enterobacteriaceae isolated from bile of patients with various clinical variants of cholangitis are presented. It was shown that bacteriocholia was registered in 53.3-90.9% of the patients during operations and in 88.9-100% of the patients during the postoperative period. Among bilicultures enterobacteria dominated (93.4% of the cases) with predominance of E. coli and Klebsiella spp. (the total about 70%). The enterobacteria isolates were frequently resistant to ampicillin and amoxycillin/clavulanate (92.6 and 70.4% of the strains respectively), gentamicin and amikacin (74.1 and 22.2%), cefazolin and cefotaxime (88.9 and 37.0%). The resistance to imipenem and ciprofloxacin (7.4%) was rare, that should be considered while prescribing drugs for empirical antimicrobial chemotherapy.

[Physico-chemical properties of staphylococci of different species in resistance to human thrombodefensins].

Testing 54 strains of staphylococci (Staphylococcus aureus, S. epidermidis, S. haemolyticus, S. warneri, S. hominis, S. capitis) revealed that S. aureus in contrast to coagulase-negative staphylococci (CNS) is more resistant to bactoriocidal action of human thrombodefensins (resistance index: 60.3 vs 25.6%), less hydrophilicolipophilic balance-HLB: -0.42 vs -0.64) and less charged (x-potential: -32.4 vs -35.6 mV). In groups of staphylococci (S. aureus and CNS) correlation links of bacterial resistance to human thrombodefensins with their HLB and x-potential (r=-0.32...-0.36). By In vitro experiments, it was shown that 5 passages of staphylococci in meat-peptonic broth with human thrombodefensins (50 mkg protein/ml) lead to adaptation of bacteria followed by the formation of resistance to cationic peptides from thrombocytes, a decrease of hydrophobicity and x-potencial. The role of physico-chemical properties in providing thrombodefensin-resistance of staphylococci as a developmental factor of infectious-and-inflammatory process and persistence of bacteria was confirmed with Salmonella infection.

[Taxonomic characterization and antibiotic resistance of pathogens of perinatal infectious inflammatory pathology in infants in Orenburg].

The materials on regional features of the nosologic structure, taxonomic spectrum and antibiotic resistance of the pathogens of perinatal infectious inflammatory pathology (IIP) in infants in Orenburg are presented. From 2002 to 2005 the average level of IIP of 19.0 cases per 1000 living new borns and the dominance of skin inflammatory diseases (vesiculopustulosis in particular) in the nosologic structure among the other forms of IIP (including conjunctivitis and pneumonia) were observed. The prevalence of the gram positive cocci with the leadership of coagulase negative staphylococci among the skin and eye forms of IIP was shown. Their portion reached 62.8%. The portion of the other microorganisms was much lover. Gramnegative bacteria (Neisseria spp., E. coli, K. ozaenae) were isolated from 6.1, 4.3 and 0.6% of the cases. The Candida isolates were detected in 1% of the cases. The regional antibiotic resistance register for the pathogens of IIP was developed. Its use is obligatory in prescribing drugs for empirical therapy of such pathology and prevention of its complications.

[Properties of Staphylococcus aureus in case of the unfavorable course of burn infection]. / Svoistva Staphylococcus aureus pri neblagopriiatnom techenii ozhogovoi infektsii.

Clinical and microbiological study of wound discharge from 35 patients demonstrated a relationship between biological properties of S. aureus, the causative agent of burn infection, and the course of the infected burn trauma. The prognostic importance of the antioxidant properties of these staphylococci was established: in cases of the unfavorable course of the burn process they showed essentially greater resistance to peroxinitrite and higher superoxide dismutase activity in comparison with the cultures isolated from patients with uncomplicated wound infection.

[Comparative analysis of the sensitivity of enterobacteria to bile]. / Sravnitel'nyi analiz chuvstvitel'nosti k zhelchi énterobacterii.

The analysis of the sensitivity of 195 enterobacterial cultures to bile revealed that their level of resistance decreased in the following row: Shigella > Salmonella > Klebsiella > Escherichia > Providencia. As shown on a sample of 136 E. coli isolates the level of resistance of these bacteria to bile depended on their isolation source: in E. coli isolated from bile in cholecystitis, from urine in pyelonephritis and from feces in intestinal dysbacteriosis resistance was 1.1-1.3 times higher than in E. coli isolated from the water of open reservoirs, from the feces of healthy persons and from extraintestinal foci of purulent inflammation. The level of sensitivity to bile is regarded as a property making it possible for enterobacteria to colonize biliary tracts and the proximal sections of the digestive tract.

[Ecovariant differences of Escherichia coli strains with respect to colicinogenicity and colicin resistance]. / Ekovariantnye otlichiia Escherichia coli po kolitsinogennosti i kolitsinoustoichivosti.

The analysis of 173 Escherichia coli strains, isolated from different sources, for colicinogenicity and colicin resistance revealed that frequency of these signs increased in the following order: water in open reservoirs, intestine, extraintestinal localizations. In most cases resistance to 5 or more bacterial colicins was due to the absence of the corresponding receptors to colicins. Colicin resistance and colicinogenicity render E. coli selective advantages under the conditions of intestinal microbiocenosis.

[Characteristics of enterobacteria isolated from patients with urogenital pathology]. / Kharakteristika énterobakterii, vydelennykh ot bol'nykh s urogenital'noi patologiei.

Species composition and a number of persistence characteristics enterobacteria isolated from urine of 42 pregnant and 22 nonpregnant women with pyelonephritis (relapse, remission), from prostatic fluid of 225 males and secretions of cervical canal of 124 women with urogenital pathology (prostatitis, salpingo-oophoritis) were studied. The study revealed that enterobacteria, including Escherichia coli, prevailed in the structure of uromicroflora (66.7-83.3%) and constituted a relatively small proportion among "genital" isolates of microorganisms (19.9-22.2%). Male and female sterility and the presence of enterobacteria in the reproductive tract of patients were found to be directly correlated. Clinical isolates of enterobacteria were shown to possess pronounced seroresistance and the complex of persistence characteristics, including antilysozyme, anti-intercidal and anticomplementary activity.

[The ecological and medical aspects of the symbiosis between Escherichia coli and man]. / Ekologicheskie i meditsinskie aspekty simbioza Escherichia coli i cheloveka.

In this work different variants of the symbiosis of E. coli with a human body are analyzed, and the symbiotic relationships between them are shown to follow the type mutualism, commensalism, parasitism and habitation. The authors emphasize that the multiplicity of variants of bacteria-host relationships is based on the phenotypic polymorphism of E. coli clones (clone lines). Taking into account their ecological (symbiotic) features and biomedical importance, all E. coli clones are divided into 4 groups (clusters): mutualists as nonpathogenic organisms; commensals as potential pathogens (causing extraintestinal E. coli infections); parasites as real pathogens (causing acute intestinal infections); "occasional" symbionts of man. The proposition on the cluster structure of E. coli as a species is formulated.

[The properties of Escherichia isolated from the bodies of mice in bacterial translocation after immobilization stress]. / Svoistva ésherikhii, vydelennykh iz organizma myshei pri bakterial'noi translokatsii posle immobilizatsionnogo stressa.

As revealed in experiments on mice, 6-hour immobilization stress initiates the process of the translocation of intestinal flora to mesenteric lymph nodes and the blood. This process is accompanied by the infection of parenchymatous organs (the liver, the spleen, the kidneys, the lungs) and the increase of the concentration of E. coli in the proximal sections of the digestive tract (the duodenum and the jejunum). As the result of the comparative analysis of the phenotypic signs of bacterial isolates obtained from intestinal and "extraintestinal" E. coli populations, the accumulation of clones with highly pronounced seroresistance and such persistence characteristics as anticomplementary and antilysozume signs, as well as resistance to the bactericidal action of leukocytic cation protein with a molecular weight of 11.0-11.5 kD, has been found to occur in the body (the blood, parenchymatous organs and the small intestine).

[The ecological determinacy of the intraspecies diversity of pathogenic bacteria]. / Ekologicheskaia determinirovannost' vnutrividovogo raznoobraziia patogennykh bakterii.

The review deals with some theoretical and applied problems of the intraspecific diversity of pathogenic microorganisms. Special attention is given to the role of ecological factors in the formation of the phenotypic polymorphism of bacteria. The possibility of using the methods of mathematical analysis for the evaluation of the influence of the environment (ecotopes) on individual phenotypic characteristics of bacteria and their complex (bioprofile) is shown. The proposition on the bioprofile of microorganisms as a criterion of their ecological (ecotopic) marking is substantiated. The examples of using the data of the ecological marking of pathogenic bacteria in clinical epidemiology and ecological practice are presented.

[Phasic changes in reproductive potential, intracellular polyamines and antilysozyme activity in Escherichia coli in periodic culture]. / Fazovye izmeneniia reproduktivnogo potentsiala, vnutrikletochnykh poliaminov i antilizotsimnoi aktivnosti u Escherichia coli v periodicheskoi kul'ture.

Growth-phase associated changes in and relationships between the specific growth rate (mu) characterizing the reproductive capacity of the cells, the contents of intracellular biogenic polyamines (BPA), such as putrescine (P), cadaverine (C), and spermidine (S), and antilysozyme activity (ALA) were studied in 37 strains of Escherichia coli grown in batch culture on solid medium. A decrease in mu upon the transition of the culture to the stationary growth phase was accompanied by a decrease in the pool of free BPA, mainly P and C, and by the appearance of ALA. The interrelations between the parameters studied were described as a complex of direct and negative correlations; the combination of low initial P and C contents, reduced P/S and C/S ratios, and a high level of ALA was designated as a factor of slight inhibition of E. coli reproduction. It is argued that BPA and ALA are integrated in a system controlling both the metabolism and stability of peptidoglycan in E. coli.

[Nonenteric escherichiosis and the problem of human reproductive health]. / Vnekishechnye ésherikhiozy i problema reproduktivnogo zdorov'ia cheloveka.

The contribution of nonenteric Escherichia infections (NEI) to the formation of male and female infertility is analyzed. The negative influence of NEI, and particularly pyelonephritis, on the course of pregnancy, parturition and the postnatal period is shown. The role of E. coli in the development of life-threatening meningoencephalitides, pneumonia, sepsis in newborn infants is emphasized, NEI risk factors are systematized with due regard to concrete stages in the pathogenesis of this pathology. Phenotypic differences between the causative agents of NEI and nonpathogenic and diarrhea-inducing E. coli are characterized.