scholarly journals Simultaneous and sequential influence of metabolite complexes of Lactobacillus rhamnosus and Saccharomyces boulardii and antibiotics against poly-resistant Gram-negative bacteria

2020 ◽  
Vol 11 (1) ◽  
pp. 139-145 ◽  
Author(s):  
O. Y. Isayenko ◽  
O. V. Knysh ◽  
O. V. Kotsar ◽  
T. N. Ryzhkova ◽  
G. I. Dyukareva

For the first time the poly-resistant strains of Gram-negative microorganisms were studied for the sensitivity to combined simultaneous and sequential influence of metabolic complexes of Lactobacillus rhamnosus GG and Saccharomyces boulardii, obtained by the author’s method without using the growth media, with antibiotics. The synergic activity of antibacterial preparations and metabolic complexes of L. rhamnosus GG and S. boulardii were studied using modified disk-diffusive method of Kirby-Bauer. During the sequential method of testing (at first the microorganisms were incubated with structural components and metabolites, then their sensitivity to the antibacterial preparations was determined), we observed increase in the diameters of the zones of growth inhibition of Pseudomonas aeruginosa PR to the typical antibiotics (gentamicin, amіcyl, ciprofloxacin, сefotaxime) and non-typical (lincomycin, levomycetin) depending on the tested combinations. Acinetobacter baumannii PR exhibited lower susceptibility: growth inhibition was seen for the combination with ciprofloxacin, сefotaxime, levomycetin. Susceptibility of Lelliottia amnigena (Enterobacter amnigenus) PR increased to levofloxacin, lincomycin. The zones of growth inhibition of Klebsiella pneumoniae PR increased to gentamicin, amіcyl, tetracycline, сeftriaxone. Maximum efficiency was determined during sequential combination of antibiotics with separate metabolic complexes of L. rhamnosus and S. boulardii, and also their combination (to 15.2, 20.2 and 15.4 mm respectively) compared with their simultaneous use (to 12.2, 15.2 and 13.0 mm respectively) for all the tested poly-resistant pathogens, regardless of the mechanism of action of antibacterial preparation. Metabolic complexes of L. rhamnosus GG and S. boulardii, due to increase in the susceptibility of microorganisms, can decrease the therapeutic concentration of antibiotic, slow the probability of the development of resistance of microorganisms, and are therefore promising candidates for developing “accompanying medications” to antibiotics and antimicrobial preparations of new generation.

2019 ◽  
Vol 10 (1) ◽  
pp. 3-8 ◽  
Author(s):  
O. Y. Isayenko ◽  
O. V. Knysh ◽  
Y. M. Babych ◽  
T. N. Ryzhkova ◽  
G. I. Dyukareva

The work presented here is the first to examine the impact of Lactobacillus rhamnosus GG ATCC 53103 and Saccharomyces boulardii metabolites obtained using the author`s method on the formation of biofilm forms of bacteria. The structural components of the probiotic microorganisms were obtained using the method of physical disintegration – low frequency ultrasound waves produced by a G3-109 generator. Metabolites were obtained by cultivating L. rhamnosus and S. boulardii in ultrasound disintegrates of lactobacteria and Saccharomycetes. The impact of biologically active substances on the formation of biofilm of Corynebacterium ulcerans tox+ 112, C. diphtheriae gravis tox+ 108, by antibiotic-resistant Pseudomonas aeruginosa PR, Klebsiella pneumoniae PR, Lelliottia amnigena (Enterobacter amnigenus) PR and P. aeruginosa AТСС 27853 reference strain was studied using the spectrophotometric method. For the first time, we proved that L. rhamnosus GG and S. boulardii metabolites and combinations of metabolites of Saccharomycetes and lactobacteria, obtained by cultivating primary producers in their disintegrates, damage preformed 24-hour biofilms of gram-positive and gram-negative bacteria. The representatives of Corynebacterium exhibited higher sensitivity to the filtrates of disintegrates and products of vital activity of lactobacteria and Saccharomycetes than gram-negative pathogens. High parameters of decrease in optical density of preformed biofilms of Corynebacterium and antibiotic-resistant gram-negative bacteria were observed under the influence of combination of L. rhamnosus GG and S. boulardii metabolites (by 1.3–2.6 times). However, the largest reduction of the optical density of the formed biofilm of all studied strains was observed under the influence of metabolites of lactobacteria (by 1.5–5.3 times). Biologically active substances of L. rhamnosus GG and S. boulardii obtained using the author’s method can be used as candidate preparations which could have a strong influence on the process of the formation of the biofilms and preformed biofilms, and also as a preparations of substitution/addition of therapeutic prescription.


2019 ◽  
Vol 10 (2) ◽  
pp. 245-250 ◽  
Author(s):  
O. Y. Isayenko ◽  
O. V. Knysh ◽  
O. V. Kotsar ◽  
T. N. Ryzhkova ◽  
G. I. Dyukareva

The article presents the results of the first study on the influence of biologically active substances Lactobacillus rhamnosus GG ATCC 53103 and Saccharomyces boulardii, obtained according to the author`s method, on growth of gram-negative bacteria with broad medical resistance: Pseudomonas aeruginosa PR, Klebsiella pneumoniae PR, Lelliottia amnigena (Enterobacter amnigenus) PR using the spectrophotometric method. Disintegrates of L. rhamnosus GG and S. boulardii were obtained using low-frequency ultrasound processing of suspension of probiotic strains, and metabolites – through cultivation of lactobacteria and saccharomycetes in disintegrates of probiotic microorganisms. To samples of test-cultures with studied filtrates of disintegrates or metabolites we added growth medium and cultivated them (period of monitoring was 5- and 24-hours). Results of the studies were expressed as the percentage of inhibition of increment in polyresistant gram-negative bacteria under the impact of biologically active substances of probiotic microorganisms. Five-hour incubation of test-strains with the studied samples of lactobacteria led to inhibition of their growth properties by 85.6–96.7%. Growth of bacteria under the impact of substances of saccharomycetes was inhibted by 45.1–92.5%. Twenty-four hour exposure of the test-cultures in filtrates of L. rhamnosus GG and S. boulardii caused 100% inhibition of P. aeruginosa and L. amnigena polyresistant strains. Temporal interval of cultivation directly proportionally affected the extent of inhibition of growth of microorganisms: we determined direct correlation dependence within 0.789–0.991. Maximum inhibition of increment of the studied pathogens was observed under the influence of metabolites of lactobacteria, obtained by cultivating primary producers in their disintegrate. We determined a high level of anti-microbial activity of metabolites from L. rhamnosus GG and S. boulardii obtained by cultivation of probiotics in disintegrates against bacteria resistant to a broad range of preparations, which allows us to consider these substances as promising for development of anti-microbial preparations of a new generation against etiologically significant antibiotic-resistant gram-negative microorganisms.


2021 ◽  
Author(s):  
Xukai Jiang ◽  
Nitin A. Patil ◽  
Mohammad A. K. Azad ◽  
Hasini Wickremasinghe ◽  
Heidi Yu ◽  
...  

Multidrug-resistant Gram-negative bacteria have been an urgent threat to global public health. Novel antibiotics are desperately needed to combat these 'superbugs'.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shira Mandel ◽  
Janna Michaeli ◽  
Noa Nur ◽  
Isabelle Erbetti ◽  
Jonathan Zazoun ◽  
...  

AbstractNew antimicrobial agents are urgently needed, especially to eliminate multidrug resistant Gram-negative bacteria that stand for most antibiotic-resistant threats. In the following study, we present superior properties of an engineered antimicrobial peptide, OMN6, a 40-amino acid cyclic peptide based on Cecropin A, that presents high efficacy against Gram-negative bacteria with a bactericidal mechanism of action. The target of OMN6 is assumed to be the bacterial membrane in contrast to small molecule-based agents which bind to a specific enzyme or bacterial site. Moreover, OMN6 mechanism of action is effective on Acinetobacter baumannii laboratory strains and clinical isolates, regardless of the bacteria genotype or resistance-phenotype, thus, is by orders-of-magnitude, less likely for mutation-driven development of resistance, recrudescence, or tolerance. OMN6 displays an increase in stability and a significant decrease in proteolytic degradation with full safety margin on erythrocytes and HEK293T cells. Taken together, these results strongly suggest that OMN6 is an efficient, stable, and non-toxic novel antimicrobial agent with the potential to become a therapy for humans.


2005 ◽  
Author(s):  
Henk V. Valkhof ◽  
Eduardo Minguito ◽  
Klaas Kooiker

As natural gas is becoming an important energy source, a large fleet is needed to transport it in liquefied form across the oceans in specially designed LNG carriers from mainly the Middle East towards the Far East. During the overall design process of such a vessel the shape of the hull form and its propulsors play an important role from a hydrodynamic point of view. This paper describes the design of a twin-gondola LNG carrier for Navantia. The twingondola aft body has proven to be an adequate design concept, but due to the complexity of the flow around the aft body the design should be carried out with great care. Computational Fluid Dynamics (CFD) tools are extremely valuable in the hydrodynamic optimization process of the hull. In this design both potential flow codes and viscous flow codes have been used to obtain the optimum hull form. With the results of the PARNASSOS viscous flow calculations it was possible to make decisions with regard to the horizontal angle and the inclination of the gondolas, and the slope of the buttocks in the area between the gondolas. Special attention has been paid to avoid flow separation around the aft body. The gondolas have been oriented in such a way that maximum efficiency is achieved. The performance of the resulting design has been verified by model tests in MARIN’s Deep Water Towing Tank. Given the very promising results of this new generation of LNG carriers, achieving besides the excellent propulsive properties also a higher payload target, the yard became more competitive and is expecting quite some orders for this particular ship type.


Author(s):  
S. B. Lysko ◽  
M. V. Zadorozhnaya ◽  
O. A. Suntsova

The modern market of drugs off ers a wide range of disinfectants. However, the constant use of the same drugs contributes to the development of resistance in the microfl ora and reduces the quality of activities. In this regard to develop eff ective measures to combat and prevent infectious diseases, it is necessary to periodically monitor the activity of disinfectants used in the enterprise. The purpose of the researches was to study the bactericidal eff ect of disinfectants on the microfl ora of poultry enterprises. The researches have been carried out at the Siberian Scientifi c and Research Institute of Poultry Farming – a branch of the Federal State Budgetary Scientifi c Institution “Omsk Agrarian Scientifi c Center”. The activity of 8 disinfectants to 37 test cultures isolated from poultry farms of diff erent productivity trends and species of poultry (chickens, turkeys, quails) has been tested. It has been found as a result of the conducted research that the most expressed bactericidal eff ect on gram-positive and gram-negative microorganisms were complex disinfectants, which included glutaraldehyde in combination with quaternary ammonium compounds. Thus, 1 % solutions of Gludesive and Viroshield provided the death of all test cultures, Dinovis Ultra and TN-4+ – 92 and 84 % of cultures. The disinfecting activity of Mirosan drug and formalin was most expressed for gram-positive microfl ora, among gram-negative microfl ora resistance was registered in 25–75 % and 25–50 % of cultures, respectively. Drugs EcoSide Advansa and Ecocide C have showed the lowest activity to all investigated microorganisms. The largest number of resistant cultures to the tested disinfectants have been registered in the bacteria of the genus Citrobacter spp. and Pseudomonas aeruginosa, while simultaneously noted resistance to 4–6 drugs.


Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 2793 ◽  
Author(s):  
Ameen Abu-Hashem

Substituted-6-methyl-1-thioxo-1,2-dihydro-3H-furo[3,2-g]pyrimido[1,6-a]quinazolin-3-ones (5a,b) were synthesized from condensation of visnagenone (2a) or khellinone (2b) with 6-amino-thiouracil (3) in dimethylformamide or refluxing of (4a) or (4b) in dimethylformamide. Hence, compounds (5a,b) were used as the starting materials for preparing many new heterocyclic compounds such as; furo[3,2-g]pyrimido[1,6-a]quinazoline (6a,b), furo[3,2-g]thiazolo[2′,3′:2,3]pyrimido[1,6-a]quinazolinone (7a,b), substituted-benzylidene-furo[3,2-g]thiazolo[2′,3′:2,3]pyrimido[1,6-a]quinazoline-3,5-dione (8a–f), 3-oxo-furo[3,2-g]pyrimido[1,6-a]quinazoline-pentane-2,4-dione (9a,b), 1-(pyrazole)-furo[3,2-g]pyrimido[1,6-a]quinazolinone (10a,b), 2-(oxo or thioxo)-pyrimidine-furo[3,2-g]pyrimido[1,6-a]quinazolinone (11a–d), 1-(methylthio)-furo[3,2-g]pyrimido[1,6-a]quinazolinone (12a,b), 1-(methyl-sulfonyl)-furo[3,2-g]pyrimido[1,6-a]quinazolinone (13a,b) and 6-methyl-1-((piperazine) or morpholino)-3H-furo[3,2-g]pyrimido[1,6-a]quinazolin-3-one (14a–d). The structures of the prepared compounds were elucidated on the basis of spectral data (IR, 1H-NMR, 13C-NMR, MS) and elemental analysis. Antimicrobial activity was evaluated for the synthesized compounds against Gram-positive, Gram-negative bacteria and fungi. The new compounds, furothiazolo pyrimido quinazolines 8a–f and 11a–d displayed results excellent for growth inhibition of bacteria and fungi.


2018 ◽  
Author(s):  
Mahmoud M. Ashawesh ◽  
Robert Markus ◽  
Christopher N. Penfold ◽  
Kim R. Hardie

AbstractBacterial infection of humans, animals and plants relies heavily on secreted proteases that degrade host defences or activate bacterial toxins. The largest family of proteins secreted by Gram-negative pathogenic bacteria, the Autotransporters (ATs), includes key proteolytic virulence factors. There remains uncertainty about the mechanistic steps of the pathway ATs share to exit bacteria, and how it is energetically driven. This study set out to shed light on the AT secretion pathway with the ultimate aim of uncovering novel antimicrobial targets that would be unlikely to trigger the development of resistance mechanisms in bacteria. To do this, two AT virulence factors with distinct proteolytic functions, EspC (secreted from EnteropathogenicEscherichia coli) and AaaA (tethered to the extracellular surface ofPseudomonas aeruginosa) were chosen. EspC and AaaA were fluorescently labelled using two separate methods to establish the localization patterns of ATs as they are secreted from a bacterial cell. Super resolution microscopy revealed that localization of ATs occurs via a helical route along the bacterial cytoskeleton. In addition to requiring the conserved C-terminal β-barrel translocator domain of the AT, we present the first evidence that secretion is dependent on a dynamic interaction with a structure reliant upon the actin homologue MreB and the Sec translocon. These findings provide a step forward in the mechanistic understanding of the secretion of this widely distributed family of proteins that have pivotal roles in bacterial pathogenesis and conserved structural properties that could serve as novel broad-range antimicrobial targets.SignificanceSecreted bacterial proteases facilitate the infection of human, animal and plant hosts by degrading host defences or activating bacterial toxins. The autotransporter family is the largest family of proteins secreted from Gram-negative bacteria, and includes proteolytic virulence factors crucial to bacterial infection. Precisely how autotransporters migrate from the inside to the outside of the cell, and how this movement is energetically driven is a mystery. We demonstrate a spiral pathway of autotransporter secretion, presenting evidence that it involves a dynamic interaction with the actin homologue MreB that comprises the bacterial cytoskeleton. Our findings open the way to unravelling the mechanism of autotransporter secretion and offer the possibility to identify novel antimicrobial targets unlikely to trigger the development of antimicrobial resistance.


2019 ◽  
Vol 4 (1) ◽  
pp. 11-16
Author(s):  
Subakhir Salnus ◽  
Nurhamsiah

This research was conducted bioactivities by using raw fruits of sapodilla sapota (Manilkara zapota) as a drag growth media of Salmonella typhi bacteria causes typhoid fever disease. Salmonella typhi is a species of bacteria that are gram-negative bacilli shaped, facultative, aerobic, moving with a single pertrich. Sapdilla sapota has antimicrobial activity against Salmonella typhi, because it contains a variety of secondary metabolite compounds such as saponins, tannins and flavonoids.  The purpose of this research was to know how efective the raw fruits of sapodilla sapota (Manilkara zapota) against the growth of Salmonella typhi. This is an laboratory research by using diffusion test method. The sample of this research is to extract the fruit of sapodilla sapota (Manilkara zapota) crude. The results of this research, are 35% concentration of extract cannot be formed drag zone (0 mm), but in 40, 45, 50 and 55% of concentration there are had drag zone (9 mm, 13 mm, 13.5 mm, and 18 mm). this can be said that the raw fruit of sapodilla sapota extract can inhibit the growth of Salmonella typhi bacteria can be done, then the next extension to the sufferers of the disease typhus to consume raw fruits of sapodilla sapota so that can reduce the growth of bacteria.


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