scholarly journals Coumarin Derivatives as New Toxic Compounds to Selected K12, R1–R4 E. coli Strains

Materials ◽  
2020 ◽  
Vol 13 (11) ◽  
pp. 2499 ◽  
Author(s):  
Paweł Kowalczyk ◽  
Arleta Madej ◽  
Daniel Paprocki ◽  
Mateusz Szymczak ◽  
Ryszard Ostaszewski

Coumarins are natural compounds that were detected in 80 species of plants. They have numerous applications including the medical, food, tobacco, perfumery, and spirit industries. They show anti-swelling and diastolic effects. However, excess consumption of coumarins may adversely affect our health, because they are easily absorbed from the intestines into the lymph and blood, causing cirrhosis of the liver. Peptidomimetics are molecules whose structure and function are similar to those of peptides. They are an important group of compounds with biological, microbiological, anti-inflammatory, and anti-cancer properties. Therefore, studies on new peptidomimetics, which load the effect of native peptides, whose half-life in the body is much longer due to structural modifications, are extremely important. A preliminary study of coumarin analogues and its derivatives as new potential antimicrobial drugs containing carboxylic acid or ester was performed to determine their basic structure related to their biological features against various types of Gram-stained bacteria by lipopolysaccharide (LPS). We hypothesized that the toxicity (antibacterial activity) of coumarin derivatives is dependent on the of LPS in bacteria and nature and position of the substituent which may be carboxylic acid, hydroxyl groups, or esters. In order to verify this hypothesis, we used K12 (smooth) and R1–R4 (rough) Escherichia coli strains which are characterized by differences in the type of LPS, especially in the O-antigen region, the outermost LPS layer. In our work, we synthesized 17 peptidomimetics containing a coumarin scaffold and checked their influence on K12 and R1–R4 E. coli strains possessing smooth and rough LPS. We also measured the damage of plasmid DNA caused by target compounds. The results of our studies clearly support the conclusion that coumarin peptidomimetics are antagonistic compounds to many of the currently used antibiotics. The high biological activity of the selected coumarin peptidomimetic was associated with identification of the so-called magic methyl groups, which substantially change the biochemical properties of target compounds. Investigating the effects of these compounds is particularly important in the era of increasingly common resistance in bacteria.

2018 ◽  
Vol 22 (2) ◽  
pp. 285-288
Author(s):  
A.P. Prevar ◽  
A.V. Kryzshanovskaya ◽  
V.A. Radionov ◽  
V.M. Mrug

The main factor in the treatment of suppurative and inflammatory processes is the timely optimization of treatment measures taking into account the nature of the microflora and its susceptibility to antimicrobial drugs. The purpose of the study is to monitor the spectrum of microorganisms – pathogens of purulent-inflammatory processes of soft tissues in surgical patients; study of the sensitivity of isolated strains to antibiotics. The material was collected in accordance with aseptic rules. The identification of a pure culture of bacteria was carried out according to morphological, culture, biochemical properties, and the presence of virulence enzymes. Sensitivity of bacteria to antibiotics was determined by the standard disks method (by Kirby-Bauer’s). 255 patients with purulent-inflammatory processes of soft tissues were examined for the period from 2014 to 2017. 229 strains of isolated bacteria were included to Escherichia coli, Citrobacer freundii, Enterobacter cloacae, E.aerogenes, Proteus vulgaris, Staphylococcus aureus, S.epidermidis, Streptococcus pyogenes, S.viridians, S.agalactiae, Pseudomonas aeruginosa. The main cause of purulent-inflammatory processes of soft tissues is Staphylococci (67,2%). Compared to previous studies, the number of P.aeruginosa isolated cultures increased (7.9%). In monoculture and in association with other microorganisms, E. coli (9.6% of cases), E.cloacae et aerogenes (3.9% of cases), P.vulgaris (3.9% of cases), C.freundi (2.5% of cases), S.agalactiae, S.pyogenes, S.viridans (3.5%). The number of associated sows reaches 12%. Clinical strains of microorganisms remain most sensitive to fluoroquinolones, cephalosporins, and also retains high sensitivity to gentamicin, lincomycin, rifampicin, which is important for empirical antibiotic therapy. To increase the effectiveness of antibacterial therapy, strict adherence to the mode of appointment of antibiotics, justification of indications, a combination of antibiotics of different spectrum of action, mandatory correction after determining the sensitivity of the pathogen.


2007 ◽  
Vol 293 (5) ◽  
pp. H2667-H2679 ◽  
Author(s):  
Charlotte Hwa ◽  
William C. Aird

In 1628, William Harvey provided definitive evidence that blood circulates. The notion that blood travels around the body in a circle raised the important question of how nutrients pass between blood and underlying tissue. Perhaps, Harvey posited, arterial blood pours into the flesh as into a sponge, only then to find its way into the veins. Far from solving this problem, Marcello Malpighi's discovery of the capillaries in 1661 only added to the dilemma: surely, some argued, these entities are little more than channels drilled into tissues around them. As we discuss in this review, it would take over 200 years to arrive at a consensus on the basic structure and function of the capillary wall. A consideration of the history of this period provides interesting insights into not only the central importance of the capillary as a focus of investigation, but also the enormous challenges associated with studying these elusive structures.


Author(s):  
О.Л. Терёхина ◽  
М.К. Нурбеков ◽  
О.П. Дмитренко ◽  
Д.М. Давыдов

С целью исследований структуры и функций белка S100B в клетке и в тканях был проведен цикл работ по оптимизации экспрессии рекомбинантного белка (рекS100B) в E. coli. Проведены процедуры аналитической экспрессии рекS100B в составе рекомбинантной плазмиды pBT7-N-His-S100B03. При SDS-ПААГЭ лизатов клонов бактерий выявлена четко экспрессирующаяся полоса в 10 кДа, которая была идентифицирована как мономерная форма белка. Перспективы исследований рекS100B связаны с потенциальным его использованием для изучения тонких молекулярных механизмов PPI взаимодействий в системе S100B/RAGE рецептор как ключевого звена передачи сигналов в клетке и организме и в качестве перспективного объекта создания диагностических систем мониторинга состояний организма в норме и при патологии связанной с нарушениями регуляции гена и/или функций S100B белка. To study structure and functions of the S100B protein in cells and tissues, a series of studies was conducted to optimize the recombinant protein (recS100B) expression in E. coli. Procedures for analytical expression of recS100B in the pBT7-N-His-S100B03 recombinant plasmid were performed. In SDS-PAGE of bacterial clone lysate, a clear 10 kDa band expression was detected, which was identified as a monomeric form of the protein. Prospects for the S100B study are related with its potential use for investigating molecular mechanisms of PPI interactions in the S100B/RAGE system as a key signal transducer in the cell and body and as a promising object for developing diagnostic systems for monitoring the body state in normal and pathological conditions associated with impaired regulation of the gene and/or functions of the S100B protein.


2019 ◽  
Author(s):  
Liam M. Rooney ◽  
William B. Amos ◽  
Paul A. Hoskisson ◽  
Gail McConnell

AbstractBiofilms are important in medicine, industry and the natural environment, however their structure is largely unexplored across multiple spatial scales. We have studied the architecture of mature Escherichia coli macro-colony biofilms by means of the Mesolens, an optical system which uniquely allows simultaneous imaging of individual bacteria and over one hundred cubic millimetres of its biofilm milieu. Our chief finding is the presence of intra-colony channels on the order of 10 μm in diameter in E. coli biofilms. These channels have a characteristic structure and reform after total mechanical disaggregation of the colony. We present evidence that the channels transport particles and function to assist the absorption of nutrients. These channels potentially offer a new route for the delivery of dispersal agents or antimicrobial drugs to biofilms, ultimately lowering their impact on public health and industry.


2020 ◽  
Vol 22 (99) ◽  
pp. 193-197
Author(s):  
R. M. Sachuk ◽  
Ya. S. Stravsky ◽  
O. A. Katsaraba ◽  
C. A. Ponomareva ◽  
N. V. Ostapiv ◽  
...  

In the nosology of obstetric pathology of goats a special place is occupied by postpartum lesions of the genitals by pathogenic microflora, of which the lion's share are postpartum vulvitis. The aim of the study was to test a new treatment regimen for postpartum vulvitis in goats and to study the therapeutic efficacy of the drug “Iodozol”, “Celexib” and “Dextrodev 50” in this pathology. Clinical and anamnestic data showed that the symptoms of postpartum vulvitis of goats were characterized by inflammatory edema, high pain, local fever, impaired tissue integrity, hematomas and discharge from the genital tract. Microbiological studies of secretions from the genitals revealed the presence of E. coli, S. aureus, less often – S. saprophyticus and E. faecalis. High resistance of microorganisms to fluoroquinolones and penicillins is noted. E. coli was sensitive to only 35.7 % of antimicrobial drugs, including ceftriaxone, ceftiofur, and iodine. S. aureus is sensitive to 49.9 % of antimicrobial drugs, including ceftriaxone, cephalexin, gentamicin, ceftiofur, iodine (highest sensitivity) and chlorhexidine. S. saprophyticus was insensitive to a number of antibiotics (oxytetracycline, gentamicin, etc.), except iodine. Taking into account microbiological researches the complex scheme of treatment of postpartum vulvitis at goats is developed. Evaluation of the effectiveness of complex therapy of this pathology in animals showed that treatment with “Iodozole”, “Celexib” and “Dextrodev 50” in a short time eliminates inflammatory symptoms (pain, infiltration, redness, discharge). At the end of the course of treatment in the blood was observed an increase in hemoglobin concentration by 13.7 %, a decrease in the number of erythrocytes by 1.7 and leukocytes by 2.2 times compared with treatment. The topical intrauterine drug “Iodozol”, a non-steroidal injectable drug “Celexib”, has been found to have a broad spectrum of antimicrobial activity, and is effective and safe to use. The drugs have an anti-edematous and analgesic effect, and symptomatic treatment with intravenous solution “Dextrodev 50” is a mandatory component of complex therapy and is aimed at replenishing the body with nutrients, as well as helps to neutralize and remove toxins from the body. Further research will be to study the clinical efficacy and develop regulations for the use of this scheme in vulvitis and cervicitis of other ruminants.


Author(s):  
M. Boublik ◽  
R.M. Wydro ◽  
W. Hellmann ◽  
F. Jenkins

Ribosomes are ribonucleoprotein particles necessary for processing the genetic information of mRNA into proteins. Analogy in composition and function of ribosomes from diverse species, established by biochemical and biological assays, implies their structural similarity. Direct evidence obtained by electron microscopy seems to be of increasing relevance in understanding the structure of ribosomes and the mechanism of their role in protein synthesis.The extent of the structural homology between prokaryotic and eukaryotic ribosomes has been studied on ribosomes of Escherichia coli (E.c.) and Artemia salina (A.s.). Despite the established differences in size and in the amount and proportion of ribosomal proteins and RNAs both types of ribosomes show an overall similarity. The monosomes (stained with 0.5% aqueous uranyl acetate and deposited on a fine carbon support) appear in the electron micrographs as round particles with a diameter of approximately 225Å for the 70S E.c. (Fig. 1) and 260Å for the 80S A.s. monosome (Fig. 2).


Author(s):  
M. Boublik ◽  
N. Robakis ◽  
J.S. Wall

The three-dimensional structure and function of biological supramolecular complexes are, in general, determined and stabilized by conformation and interactions of their macromolecular components. In the case of ribosomes, it has been suggested that one of the functions of ribosomal RNAs is to act as a scaffold maintaining the shape of the ribosomal subunits. In order to investigate this question, we have conducted a comparative TEM and STEM study of the structure of the small 30S subunit of E. coli and its 16S RNA.The conventional electron microscopic imaging of nucleic acids is performed by spreading them in the presence of protein or detergent; the particles are contrasted by electron dense solution (uranyl acetate) or by shadowing with metal (tungsten). By using the STEM on freeze-dried specimens we have avoided the shearing forces of the spreading, and minimized both the collapse of rRNA due to air drying and the loss of resolution due to staining or shadowing. Figure 1, is a conventional (TEM) electron micrograph of 30S E. coli subunits contrasted with uranyl acetate.


Author(s):  
M. Boublik ◽  
W. Hellmann ◽  
F. Jenkins

Correlations between structure and function of biological macromolecules have been studied intensively for many years, mostly by indirect methods. High resolution electron microscopy is a unique tool which can provide such information directly by comparing the conformation of biopolymers in their biologically active and inactive state. We have correlated the structure and function of ribosomes, ribonucleoprotein particles which are the site of protein biosynthesis. 70S E. coli ribosomes, used in this experiment, are composed of two subunits - large (50S) and small (30S). The large subunit consists of 34 proteins and two different ribonucleic acid molecules. The small subunit contains 21 proteins and one RNA molecule. All proteins (with the exception of L7 and L12) are present in one copy per ribosome.This study deals with the changes in the fine structure of E. coli ribosomes depleted of proteins L7 and L12. These proteins are unique in many aspects.


2020 ◽  
Vol 27 (3) ◽  
pp. 201-209
Author(s):  
Syed Saqib Ali ◽  
Mohammad Khalid Zia ◽  
Tooba Siddiqui ◽  
Haseeb Ahsan ◽  
Fahim Halim Khan

Background: Ascorbic acid is a classic dietary antioxidant which plays an important role in the body of human beings. It is commonly found in various foods as well as taken as dietary supplement. Objective: The plasma ascorbic acid concentration may range from low, as in chronic or acute oxidative stress to high if delivered intravenously during cancer treatment. Sheep alpha-2- macroglobulin (α2M), a human α2M homologue is a large tetrameric glycoprotein of 630 kDa with antiproteinase activity, found in sheep’s blood. Methods: In the present study, the interaction of ascorbic acid with alpha-2-macroglobulin was explored in the presence of visible light by utilizing various spectroscopic techniques and isothermal titration calorimetry (ITC). Results: UV-vis and fluorescence spectroscopy suggests the formation of a complex between ascorbic acid and α2M apparent by increased absorbance and decreased fluorescence. Secondary structural changes in the α2M were investigated by CD and FT-IR spectroscopy. Our findings suggest the induction of subtle conformational changes in α2M induced by ascorbic acid. Thermodynamics signatures of ascorbic acid and α2M interaction indicate that the binding is an enthalpy-driven process. Conclusion: It is possible that ascorbic acid binds and compromises antiproteinase activity of α2M by inducing changes in the secondary structure of the protein.


Author(s):  
Steven N. Dworkin

This book describes the linguistic structures that constitute Medieval or Old Spanish as preserved in texts written prior to the beginning of the sixteenth century. It emphasizes those structures that contrast with the modern standard language. Chapter 1 presents methodological issues raised by the study of a language preserved only in written sources. Chapter 2 examines questions involved in reconstructing the sound system of Old Spanish before discussing relevant phonetic and phonological details. The chapter ends with an overview of Old Spanish spelling practices. Chapter 3 presents in some detail the nominal, verbal, and pronominal morphology of the language, with attention to regional variants. Chapter 4 describes selected syntactic structures, with emphasis on the noun phrase, verb phrase, object pronoun placement, subject-verb-object word order, verb tense, aspect, and mood. Chapter 5 begins with an extensive list of Old Spanish nouns, adjectives, verbs, and function words that have not survived into the modern standard language. It then presents examples of coexisting variants (doublets) and changes of meaning, and finishes with an overview of the creation of neologisms in the medieval language through derivational morphology (prefixation, suffixation, compounding). The book concludes with an anthology composed of three extracts from Spanish prose texts, one each from the thirteenth, fourteenth, and fifteenth centuries. The extracts contain footnotes that highlight relevant morphological, syntactic, and lexical features, with cross references to the relevant sections in the body of the book.


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