scholarly journals Evaluation of Seaweed Sulfated Polysaccharides As Natural Antagonists Targeting Salmonella typhi OmpF: Molecular Docking and Pharmacokinetic Profiling

Author(s):  
ARUN KUMAR MALAISAMY ◽  
Mahalakshmi Murugan ◽  
Ashok Kumar Vairamuthu ◽  
Manikka Kubendran Aravind ◽  
Sathaiah Gunaseelan ◽  
...  

Abstract Background: Salmonella belongs to the Enterobacteriaceae family, a gram-negative, non-spore-forming, rod-shaped, motile, and pathogenic bacteria that transmit through unhygienic conditions. It is estimated that 21 million new infections arise every year, resulting in approximately 200,000 deaths. It is more prevalent among children, the old aged, and immunocompromised individuals. The frequent usage of classical antimicrobials has begun the increasing emergence of various drug-resistant pathogenic bacterial strains. Hence, this study was intended to evaluate the bioactive seaweed sulfated polysaccharides (SSP) against the ompF (outer membrane porin F) protein target of Salmonella typhi. SSP are sulfated compounds with a wide range of biological activities, such as anti-microbial, anti-allergy, anti-cancer, anti-coagulant, anti-inflammation, anti-oxidant, and anti-viral. Results: In this study, eleven compounds were targeted against S. typhi OmpF by molecular docking approach and were compared with two commercially available typhoid medications. The SSP showed good binding affinity compared to commercial drugs, particularly carrageenan/MIV-150, carrageenan lambda, fucoidan, and 3-Phenyllactate, ranked as top antagonists against OmpF. Further, pharmacokinetics and toxicology (ADMET) studies corroborated that SSP possessed drug-likeness and highly progressed in all parameters.Conclusion: AutoDockTools and Schrodinger's QikProp module results suggest that SSP could be a promising drug for extensively drug-resistant (XDR) S. typhi. To our best of knowledge, this is the first report on in-silico analysis of SSP against S. typhi OmpF. Thus, implying the capabilities of SSP's especially compounds like carrageenans, as a potential anti-microbial agent against Salmonella typhi infections. Eventually, advanced studies could corroborate SSPs to the next level of application in the crisis of XDR microbial diseases.

Author(s):  
Malaisamy Arunkumar ◽  
Murugan Mahalakshmi ◽  
Vairamuthu Ashokkumar ◽  
Manikka Kubendran Aravind ◽  
Sathaiah Gunaseelan ◽  
...  

Abstract Background Salmonella belongs to the Enterobacteriaceae family, a gram-negative, non-spore-forming, rod-shaped, motile, and pathogenic bacteria that transmit through unhygienic conditions. It is estimated that 21 million new infections arise every year, resulting in approximately 200,000 deaths. It is more prevalent among children, the old aged, and immunocompromised individuals. The frequent usage of classical antimicrobials has begun the increasing emergence of various drug-resistant pathogenic bacterial strains. Hence, this study was intended to evaluate the bioactive seaweed sulfated polysaccharides (SSPs) against the ompF (outer membrane porin F) protein target of Salmonella typhi. SSP is the sulfated compound with a wide range of biological activities, such as anti-microbial, anti-allergy, anti-cancer, anti-coagulant, anti-inflammation, anti-oxidant, and anti-viral. Results In this study, eleven compounds were targeted against S. typhi OmpF by the molecular docking approach and were compared with two commercially available typhoid medications. The SSP showed good binding affinity compared to commercial drugs, particularly carrageenan/MIV-150, carrageenan lambda, fucoidan, and 3-phenyllactate, ranked as top antagonists against OmpF. Further, pharmacokinetics and toxicology (ADMET) studies corroborated that SSP possessed drug-likeness and highly progressed in all parameters. Conclusions AutoDockTools and Schrodinger's QikProp module results suggest that SSP could be a promising drug for extensively drug-resistant (XDR) S. typhi. To the best of our knowledge, this is the first report on in silico analysis of SSP against S. typhi OmpF, thus implying the capabilities of SSPs especially compounds like carrageenans, as a potential anti-microbial agent against Salmonella typhi infections. Eventually, advanced studies could corroborate SSPs to the next level of application in the crisis of XDR microbial diseases. Graphical Abstract


2021 ◽  
Vol 20 (11) ◽  
pp. 2363-2370
Author(s):  
Amir Saeed ◽  
Khalid Alshaghdali ◽  
Mohd Saeed ◽  
Mousa Alreshidi

Purpose: To explore the potency of FimH inhibitors against CTX-M β-lactamase enzyme type 15, in view of the increasing prevalence of CTX-M 15 in uropathogenic strains which has reduced the treatment options to minimal.Method: FimH inhibitors were targeted against CTXM-15 by a molecular docking approach. Thereafter, the best ligand-target confirmation was selected and analyzed using LIGPLOT+ Version v.2.1. The hydrophobic and hydrogen bonding among the catalytic site amino acids of CTXM-15 and the FimH inhibitors were analyzed and 3-D structures were converted into 2-D images by LIGPLOT algorithm.Results: Out of all the FimH inhibitors tested, 3′-chloro-4′- (α-D-mannopyranosyloxy) biphenyl-4- carbonitrile, para-biphenyl-2-methyl-3′-methylamidemannoside, para-biphenyl-2-methyl-3′,5′dimethylamide-α-D-mannoside, and thiazolylamino mannoside exhibited better interaction with the CTX-M15 active site than the positive control avibactam. Moreover, in CTX-M 15, the amino acid residues, Ser70, Tyr105, Ser130, Asn132, Thr216, Thr235, Gly236, and Ser237 were commonly interacting with these FimH inhibitors as well as avibactam.Conclusion: The predicted findings suggest that these FimH inhibitors could be explored as potential CTX-M 15 inhibitors to cope-up with resistance issues of uropathogenic bacteria in the form of an alternate strategy.


Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 717
Author(s):  
Rita Abou Nader ◽  
Rawan Mackieh ◽  
Rim Wehbe ◽  
Dany El El Obeid ◽  
Jean Marc Sabatier ◽  
...  

Honeybees are one of the most marvelous and economically beneficial insects. As pollinators, they play a vital role in every aspect of the ecosystem. Beehive products have been used for thousands of years in many cultures for the treatment of various diseases. Their healing properties have been documented in many religious texts like the Noble Quran and the Holy Bible. Honey, bee venom, propolis, pollen and royal jelly all demonstrated a richness in their bioactive compounds which make them effective against a variety of bacterial strains. Furthermore, many studies showed that honey and bee venom work as powerful antibacterial agents against a wide range of bacteria including life-threatening bacteria. Several reports documented the biological activities of honeybee products but none of them emphasized on the antibacterial activity of all beehive products. Therefore, this review aims to highlight the antibacterial activity of honey, bee venom, propolis, pollen and royal jelly, that are produced by honeybees.


2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Ashraf A. Mostafa ◽  
Shaban R. M. Sayed ◽  
Essam N. Solkamy ◽  
Mujeeb Khan ◽  
Mohammed Rafi Shaik ◽  
...  

Silver nanoparticles were synthesized by the earlier reported methods. The synthesized nanoparticles were characterized using ultraviolet-visible spectrophotometry (UV/Vis), transmission electron microscopy (TEM), energy dispersive X-ray spectroscopy (EDX), and X-ray powder diffraction (XRD). The synthesized materials were also evaluated for their antibacterial activity against Gram positive and Gram negative bacterial strains. TEM micrograph showed the spherical morphology of AgNPs with size range of 40–60 nm.The synthesized nanoparticles showed a strong antimicrobial activity and their effect depends upon bacterial strain as AgNPs exhibited greater inhibition zone forPseudomonas aeruginosa(19.1 mm) followed byStaphylococcus aureus(14.8 mm) andS. pyogenes(13.6 mm) while the least activity was observed forSalmonella typhi(12.5 mm) at concentration of 5 µg/disc. The minimum inhibitory concentration (MIC) of AgNPs againstS. aureuswas 2.5 µg/disc and less than 2.5 µg/disc forP. aeruginosa. These results suggested that AgNPs can be used as an effective antiseptic agent for infectious control in medical field.


2022 ◽  
Author(s):  
Kokab Jabeen ◽  
Sidrah Saleem ◽  
Faiqa Arshad ◽  
Zill-e-Huma ◽  
Shah Jahan ◽  
...  

Abstract Typhoid fever is a significant health problem in developing countries like Pakistan. Salmonella Typhi the causative agent of typhoid has developed resistant to almost all recommended antibiotics. Emergence of resistance to third generation cephalosporins has further complicated the situation and such strains are called as extensively drug resistant (XDR) Salmonella Typhi. Currently only available options are azithromycin and cabapenems. Recently few reports of azithromycin resistance have emerged from countries like Pakistan, India, Bangladesh and Nepal. As azithromycin is the only oral option available to treat XDR Typhoid, development of resistance may change treatment strategy altogether from out patient management to hospitalization of every patient. This may increase the burden on already weak health care system of countries like Pakistan. So there is dire need to look for the alternative treatment options. Manuka honey is well known for its therapeutic potential against wide range of bacteria including Salmonella Typhimurium. In this study 3 azithromycin resistant isolates were isolated and identified using disc diffusion, E-test and broth micro dilution methods and antibacterial activity, MIC and MBC of manuka honey was performed by agar well diffusion assay and broth micro dilution assay respectively. Manuka honey manifested significant antibacterial activity against all test isolates with zone of inhibition ranging from 7.3mm to 7.5mm, MIC and MBC values were between 10 to 15% v/v Here, we conclude that Manuka honey possess potent antibacterial activity and might be used as an alternative treatment option against azithromycin resistant XDR Typhid. However, further clinical trials are mandatory to validate our initial findings.


Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 4817
Author(s):  
Huda R. M. Rashdan ◽  
Ihsan A. Shehadi ◽  
Mohamad T. Abdelrahman ◽  
Bahaa A. Hemdan

In this study, a new synthetic 1,2,3-triazole-containing disulfone compound was derived from dapsone. Its chemical structure was confirmed using microchemical and analytical data, and it was tested for its in vitro antibacterial potential. Six different pathogenic bacteria were selected. MICs values and ATP levels were determined. Further, toxicity performance was measured using MicroTox Analyzer. In addition, a molecular docking study was performed against two vital enzymes: DNA gyrase and Dihydropteroate synthase. The results of antibacterial abilities showed that the studied synthetic compound had a strong bactericidal effect against all tested bacterial strains, as Gram-negative species were more susceptible to the compound than Gram-positive species. Toxicity results showed that the compound is biocompatible and safe without toxic impact. The molecular docking of the compound showed interactions within the pocket of two enzymes, which are able to stabilize the compound and reveal its antimicrobial activity. Hence, from these results, this study recommends that the established compound could be an outstanding candidate for fighting a broad spectrum of pathogenic bacterial strains, and it might therefore be used for biomedical and pharmaceutical applications.


2020 ◽  
Vol 17 (36) ◽  
pp. 18-31
Author(s):  
Ahmad khadem HACHIM ◽  
Rashid Rahim HATEET ◽  
Tawfik Muhammad MUHSIN

The purpose of the present work aimed at exploring the potential biochemical components and biological activities of an organic extract of the white truffle Tirmania nivea collected from the Iraqi desert, then test the organic extract against the Cytotoxicity on Human Larynx carcinoma cells and selected strains of pathogenic bacteria. Fourier transform infrared spectroscopy (FTIR) and gas chromatography-mass spectrometry GC/MSS were used to analyze mycochemical compositions. The antibacterial activity and Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) was investigated using a disk diffusion agar method. The truffle extract's cytotoxicity effect against the larynx cell line (Hep-2) was assessed by the MTT assay (in vitro). FTIR results provided the presence of phenol, carboxylic acid, and alkane's functional group, The GC-MS analysis of T. nivea disclose the existence of nineteen compounds that can contribute to the pharmaceutical properties of the truffle. As for antibacterial activity result, A growth inhibition activity of truffle extract at (18-40 mm inhibition zones) against the tested pathogenic bacterial strains was detected, which minimum inhibitory concentration values ranged from 3.12 to 6.25 mg/mL for Escherichia coli (ATCC 25922) and Staphylococcus aureus (ATCC 25923) Respectively. The results of cytotoxicity shown that the organic truffle extract exhibited a high inhibitory rate (52.685%) against cell line (Hep-2) at a concentration of 1.56 ?g/mL. In this work, the results showed that the organic extracts of T. nivea are very promising as cancer cytotoxicity and antibacterial agent for future medical applications.


2019 ◽  
Vol 2 (1) ◽  
pp. 20-23
Author(s):  
Yoni Rina Bintari ◽  
Rio Risandiansyah

Increasing antibiotic-resistant pathogenic bacteria is a severe problem in the world. Therefore, there is a need to identify new drugs from natural products and also new drug targets. Cladophora sp. is a marine organism which is known to have bioactive compounds and a potential antibacterial. On the other hand, Peptide Deformylase (PDf) may prove to be a novel drug target since it is crucial for native peptide functioning in most pathogenic bacteria. This study screens for PDf inhibition activity of compounds from Cladophora sp. using molecular docking approach and screening the binding affinity of bioactive compounds against the peptide receptor PDf using Pyrex Autodock Vina software. Docking results were stored and visualized using Biovia Discovery Studio and PyMOL ligand. Ligands were obtained from previous literature in PubChem, and receptor peptide PDf from pathogenic bacteria: Pseudomonas aeruginosa (PDB ID:1N5N), Escherichia coli (PDB ID:1BSK), Enterococcus faecium (PDB ID:3G6N) and Staphylococcus aureus (PDB ID:1LQW), was obtained from the peptide data bank. The results of this screening show with ligand the highest binding affinity against PDf of P. aeruginosa, E. coli, E. faecium, and S. aureus is stearic acid (-5.9 kcal/mol), eicosapentaenoic acid (-6.6 kcal/mol), stearic acid (-5.8 kcal/mol), and stearic acid (-6.2 kcal/mol) respectively. The binding of natural compounds from Cladophora sp. with PDf models may provide a new drug with a different drug target for antibacterial potential.


2018 ◽  
Vol 22 (6) ◽  
pp. 667-675 ◽  
Author(s):  
T. I. Odintsova ◽  
M. P. Slezina ◽  
E. A. Istomina

Antimicrobial peptides (AMPs) are important components of defense system in both plants and animals. They represent an ancient mechanism of innate immunity providing rapid first line of defense against pathogens. Plant AMPs are classified into several families: thionins, defensins, nonspecific lipid-transfer proteins, hevein- and knottin-type peptides, hairpinins and macrocyclic peptides (cyclotides). The review focuses on the thionin family. Thionins comprise a plant-specific AMP family that consists of short (~5 kDA) cysteine-rich peptides containing 6 or 8 cysteine residues with antimicrobial and toxic properties. Based on similarity in amino acid sequences and the arrangement of disulphide bonds, five structural classes of thionins are discriminated. The three-dimensional structures of a number of thionins were determined. The amphipathic thionin molecule resembles the Greek letter Г, in which the long arm is formed by two antiparallel α-helices, while the short one, by two parallel β-strands. The residues responsible for the antimicrobial activity of thionins were identified. Thionins are synthesized as precursor proteins consisting of a signal peptide, the mature peptide region and the C-terminal prodomain. Thionins protect plants from pathogenic bacteria and fungi acting directly on the membranes of microorganisms at micromolar concentrations, although their precise mode of action remains unclear. In addition to plant pathogens, thionins inhibit growth of a number of human pathogens and opportunistic microorganisms, such as Candida spp., Saccharomyces cerevisiae, Fusarium solani, Staphylococcus aureus and Escherichia coli. Thionins are toxic to different types of cells including mammalian cancer cell lines. Transgenic plants expressing thionin genes display enhanced resistance to pathogens. A wide range of biological activities makes thionins promising candidates for practical application in agriculture and medicine.


1970 ◽  
Vol 2 (2) ◽  
pp. 31-34 ◽  
Author(s):  
Mst Jesmin Sultana ◽  
Md Tamzid Hossain Molla ◽  
MT Alam ◽  
Fazle Rabbi Shakil Ahmed

Biological activities of fresh stem of the plant Swertia chirata Ham. (F. Gentianaceae) extracted in rectified spirit is reported here. The crude rectified spirit extract was fractionated by using standard chromatographic techniques on alumina, which gave six fractions (A, B, C, D, E & F). When subjected to column chromatographic analysis on neutral alumina, fraction D yielded a pure compound tentatively known as AJ-1 that have melting point of 178° C. AJ-1 was screened for its antibacterial activities against 12 pathogenic bacteria, 6 Gram positive and 6 Gram negative, by disc diffusion method at a concentration of 200 μg/disc. The results obtained were compared with those for a standard antibiotic Kanamycin. AJ-1 showed significant activity against Bacillus megaterium (11 mm), Bacillus subtilis (9 mm), Salmonella typhi-A (10 mm), Shigella flexeneriae (10 mm) and Klebsiella sp (11 mm) but a little activity against Staphylococcus aureus. The Minimum Inhibitory Concentrations (MIC) of AJ-1 determined against Bacillus megaterium and Salmonella typhi-A were 128 μg/ml and 128 μg/ml, respectively when tested in a nutrient broth medium. AJ-1 also showed significant activity against the brine shrimp (Artemia salina) nauplii (LC50 value of 9.34 μg/ml), in which the mortality rate increased with the increasing concentration of the compound, suggesting a positive correlation between brine shrimp toxicity and cytotoxicity. Key words: Biological activity; Swertia chirata; Gentianaceae; pathogenic bacteria DOI: 10.3329/jles.v2i2.7494 J. Life Earth Sci., Vol. 2(2) 31-34, 2007


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