scholarly journals In Silico/In Vitro Strategies Leading to the Discovery of New Nonribosomal Peptide and Polyketide Antibiotics Active against Human Pathogens

2021 ◽  
Vol 9 (11) ◽  
pp. 2297
Author(s):  
Sami Khabthani ◽  
Jean-Marc Rolain ◽  
Vicky Merhej
Keyword(s):  
In Silico ◽  
High Throughput Sequencing ◽  
Human Pathogens ◽  
Nonribosomal Peptide ◽  
Culture Techniques ◽  
Antimicrobial Substances ◽  
Potential Source ◽  
Antibiotic Compounds ◽  
Antibiotic Discovery

Antibiotics are majorly important molecules for human health. Following the golden age of antibiotic discovery, a period of decline ensued, characterised by the rediscovery of the same molecules. At the same time, new culture techniques and high-throughput sequencing enabled the discovery of new microorganisms that represent a potential source of interesting new antimicrobial substances to explore. The aim of this review is to present recently discovered nonribosomal peptide (NRP) and polyketide (PK) molecules with antimicrobial activity against human pathogens. We highlight the different in silico/in vitro strategies and approaches that led to their discovery. As a result of technological progress and a better understanding of the NRP and PK synthesis mechanisms, these new antibiotic compounds provide an additional option in human medical treatment and a potential way out of the impasse of antibiotic resistance.

Enhancing microbiological safety of water and food

2014 ◽  
Author(s):  
◽  
Zhenyu Shen
Keyword(s):  
16S Rdna ◽  
In Silico ◽  
Mung Bean ◽  
Disease Outbreaks ◽  
Laboratory Strain ◽  
Human Pathogens ◽  
University Of Missouri ◽  
Enterohaemorrhagic Escherichia Coli ◽  
Wastewater Samples

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Human and animal feces are the main sources of pathogens associated with foodborne and waterborne disease outbreaks. The studies in Volume I proposed ribosomal intervening sequences (IVSs) can be used as host-specific genetic markers for tracking fecal sources in polluted food and water. In Chapter 3, using bioinformatics tools, one IVS in Faecalibacterium 16S rDNA specific to poultry (chicken and turkey) was identified in silico. A PCR assay was then developed to confirm the IVS was only present in fecal or wastewater samples from poultry. The study in Chapter 4 comprehensively examined host specificities of IVSs in 16S rDNA of 73 genera of fecal bacteria. A total of 13 IVSs were identified to be associated particular host sources in silico and the host-specificities of eight of them were confirmed by PCR reactions. Furthermore, a novel beef cattle-specific IVS was identified with next generation sequencing (NGS). Internalization of human pathogens in produce poses high risks to human health because the surface-sanitization method fail to inactivate the pathogens. The study in Volume II proposed to control the pathogen internalization with endophytic Bacillus subtilis strains isolated from vegetables. Twelve endophytic B. subtilis strains isolated from inner tissue of lettuce stems and mung bean seeds displayed inhibitory activity against a Salmonella enterica indicator in vitro and two of them (LCA1 and M24) showed broad inhibitory spectrums. LCA1, M24, and a laboratory strain B. subtilis 168 could internalize in mung bean sprouts and significantly reduced the internalization of S. enterica and enterohaemorrhagic Escherichia coli (EHEC).

scholarly journals Synthesis, Biological Assessment, and Structure Activity Relationship Studies of New Flavanones Embodying Chromene Moieties

Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 544 ◽  
Author(s):  
Eman Assirey ◽  
Azhaar Alsaggaf ◽  
Arshi Naqvi ◽  
Ziad Moussa ◽  
Rawda M. Okasha ◽  
...  
Keyword(s):  
In Silico ◽  
Biological Assessment ◽  
Diffusion Method ◽  
Breast Adenocarcinoma ◽  
Cytotoxic Activities ◽  
Human Pathogens ◽  
Bacterial Strains ◽  
Human Carcinoma ◽  
In Silico Studies

Novel flavanones that incorporate chromene motifs are synthesized via a one-step multicomponent reaction. The structures of the new chromenes are elucidated by using IR, 1H-NMR, 13C-NMR, 1H-1H COSY, HSQC, HMBC, and elemental analysis. The new compounds are screened for their in vitro antimicrobial and cytotoxic activities. The antimicrobial properties are investigated and established against seven human pathogens, employing the agar well diffusion method and the minimum inhibitory concentrations. A majority of the assessed derivatives are found to exhibit significant antimicrobial activities against most bacterial strains, in comparison to standard reference drugs. Moreover, their cytotoxicity is appraised against four different human carcinoma cell lines: human colon carcinoma (HCT-116), human hepatocellular carcinoma (HepG-2), human breast adenocarcinoma (MCF-7), and adenocarcinoma human alveolar basal epithelial cell (A-549). All the desired compounds are subjected to in-silico studies, forecasting their drug likeness, bioactivity, and the absorption, distribution, metabolism, and excretion (ADME) properties prior to their synthetic assembly. The in-silico molecular docking evaluation of all the targeted derivatives is undertaken on gyrase B and the cyclin-dependent kinase. The in-silico predicted outcomes were endorsed by the in vitro studies.

scholarly journals In Vitro and In Silico Approaches for the Evaluation of Antimicrobial Activity, Time-Kill Kinetics, and Anti-Biofilm Potential of Thymoquinone (2-Methyl-5-propan-2-ylcyclohexa-2,5-diene-1,4-dione) against Selected Human Pathogens

Antibiotics ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 79
Author(s):  
Kamal A. Qureshi ◽  
Mahrukh Imtiaz ◽  
Adil Parvez ◽  
Pankaj K. Rai ◽  
Mariusz Jaremko ◽  
...  
Keyword(s):  
Candida Albicans ◽  
In Silico ◽  
Xylose Reductase ◽  
Human Pathogens ◽  
Target Proteins ◽  
Antimicrobial Potential ◽  
Antibacterial And Antifungal ◽  
In Silico Molecular Docking ◽  
Time Kill

Thymoquinone (2-methyl-5-propan-2-ylcyclohexa-2,5-diene-1,4-dione; TQ), a principal bioactive phytoconstituent of Nigella sativa essential oil, has been reported to have high antimicrobial potential. Thus, the current study evaluated TQ’s antimicrobial potential against a range of selected human pathogens using in vitro assays, including time-kill kinetics and anti-biofilm activity. In silico molecular docking of TQ against several antimicrobial target proteins and a detailed intermolecular interaction analysis was performed, including binding energies and docking feasibility. Of the tested bacteria and fungi, S. epidermidis ATCC 12228 and Candida albicans ATCC 10231 were the most susceptible to TQ, with 50.3 ± 0.3 mm and 21.1 ± 0.1 mm zones of inhibition, respectively. Minimum inhibitory concentration (MIC) values of TQ are in the range of 12.5–50 µg/mL, while minimum biocidal concentration (MBC) values are in the range of 25–100 µg/mL against the tested organisms. Time-kill kinetics of TQ revealed that the killing time for the tested bacteria is in the range of 1–6 h with the MBC of TQ. Anti-biofilm activity results demonstrate that the minimum biofilm inhibitory concentration (MBIC) values of TQ are in the range of 25–50 µg/mL, while the minimum biofilm eradication concentration (MBEC) values are in the range of 25–100 µg/mL, for the tested bacteria. In silico molecular docking studies revealed four preferred antibacterial and antifungal target proteins for TQ: D-alanyl-D-alanine synthetase (Ddl) from Thermus thermophilus, transcriptional regulator qacR from Staphylococcus aureus, N-myristoyltransferase from Candida albicans, and NADPH-dependent D-xylose reductase from Candida tenuis. In contrast, the nitroreductase family protein from Bacillus cereus and spore coat polysaccharide biosynthesis protein from Bacillus subtilis and UDP-N-acetylglucosamine pyrophosphorylase from Aspergillus fumigatus are the least preferred antibacterial and antifungal target proteins for TQ, respectively. Molecular dynamics (MD) simulations revealed that TQ could bind to all four target proteins, with Ddl and NADPH-dependent D-xylose reductase being the most efficient. Our findings corroborate TQ’s high antimicrobial potential, suggesting it may be a promising drug candidate for multi-drug resistant (MDR) pathogens, notably Gram-positive bacteria and Candida albicans.

scholarly journals In Silico Screening and In Vitro Assessment of Natural Products with Anti-Virulence Activity against Helicobacter pylori

Molecules ◽  
2021 ◽  
Vol 27 (1) ◽  
pp. 20
Author(s):  
Maciej Spiegel ◽  
Paweł Krzyżek ◽  
Ewa Dworniczek ◽  
Ryszard Adamski ◽  
Zbigniew Sroka
Keyword(s):  
Helicobacter Pylori ◽  
In Silico ◽  
Stringent Response ◽  
Human Pathogens ◽  
Gastric Diseases ◽  
Natural Substances ◽  
Interesting Candidate ◽  
H Pylori ◽  
Static Conditions

Helicobacter pylori is one of the most frequent human pathogens and a leading etiological agent of various gastric diseases. As stringent response, coordinated by a SpoT protein, seems to be crucial for the survivability of H. pylori, the main goal of this article was to use in silico computational studies to find phytochemical compounds capable of binding to the active site of SpoT from H. pylori and confirm the ability of the most active candidates to interfere with the virulence of this bacterium through in vitro experiments. From 791 natural substances submitted for the virtual screening procedure, 10 were chosen and followed for further in vitro examinations. Among these, dioscin showed the most interesting parameters (the lowest MIC, the highest anti-biofilm activity in static conditions, and a relatively low stimulation of morphological transition into coccoids). Therefore, in the last part, we extended the research with a number of further experiments and observed the ability of dioscin to significantly reduce the formation of H. pylori biofilm under Bioflux-generated flow conditions and its capacity for additive enhancement of the antibacterial activity of all three commonly used antibiotics (clarithromycin, metronidazole, and levofloxacin). Based on these results, we suggest that dioscin may be an interesting candidate for new therapies targeting H. pylori survivability and virulence.

scholarly journals Herpes simpex virus 2 (HSV-2) evolves faster in cell culture than HSV-1 by generating greater genetic diversity

2021 ◽  
Author(s):  
Alberto D. López-Muñoz ◽  
Alberto Rastrojo ◽  
Rocío Martín ◽  
Antonio Alcami
Keyword(s):  
Genetic Diversity ◽  
High Throughput Sequencing ◽  
De Novo ◽  
Culture Conditions ◽  
Evolutionary Divergence ◽  
Human Pathogens ◽  
Selective Pressures ◽  
Hsv 1

Herpes simplex virus type 1 and 2 (HSV-1 and HSV-2, respectively) are prevalent human pathogens of clinical relevance that establish long-life latency in the nervous system. They have been considered, along with the Herpesviridae family, to exhibit a low level of genetic diversity during viral replication. However, the high ability shown by these viruses to rapidly evolve under different selective pressures does not correlates with that presumed genetic stability. High-throughput sequencing has revealed that heterogeneous or plaque-purified populations of both serotypes contain a broad range of genetic diversity, in terms of number and frequency of minor genetic variants, both in vivo and in vitro . This is reminiscent of the quasispecies phenomenon traditionally associated with RNA viruses. Here, by plaque-purification of two selected viral clones of each viral subtype, we reduced the high level of genetic variability found in the original viral stocks, to more genetically homogeneous populations. After having deeply characterized the genetic diversity present in the purified viral clones as a high confidence baseline, we examined the generation of de novo genetic diversity under culture conditions. We found that both serotypes gradually increased the number of de novo minor variants, as well as their frequency, in two different cell types after just five and ten passages. Remarkably, HSV-2 populations displayed a much higher raise of nonconservative de novo minor variants than the HSV-1 counterparts. Most of these minor variants exhibited a very low frequency in the population, increasing their frequency over sequential passages. These new appeared minor variants largely impacted the coding diversity of HSV-2, and we found some genes more prone to harbor higher variability. These data show that herpesviruses generate de novo genetic diversity differentially under equal in vitro culture conditions. This might have contributed to the evolutionary divergence of HSV-1 and HSV-2 adapting to different anatomical niche, boosted by selective pressures found at each epithelial and neuronal tissue.

In-vitro and In-silico analysisof anti-diabetic and anti-microbial activity of Cichorium intybus leaf extracts

2020 ◽  
Vol 16 ◽  
Author(s):  
Suganya Ramakrishnamurthy ◽  
Ganesan Singaravelu ◽  
Velmurugan Devadasan ◽  
Aruna Prakasarao
Keyword(s):  
In Silico ◽  
Ethanolic Extract ◽  
Ethanol Extract ◽  
Docking Studies ◽  
Human Pathogens ◽  
Leaf Extracts ◽  
Ligand Complex ◽  
Dynamic Simulations ◽  
In Silico Studies

Objective: To screen the selected phytochemicals against diabetes by docking studies in comparison with experimental analysis. Methods: Ethanol crude extract has been obtained from the leaves of C.intybus and its chemical compounds were identified using GC- MS. Docking studies were carried out for selected phytochemicals to find the binding affinity and H-bond interaction using Scrodinger suite. Dynamic simulations were carried out for protein ligand complex up to 50ns using desmond OPLS AA forcefield and α- Amylase and α- Glucosidase assay were carried for ethanolic extract to infer its inhibition. Results: Four compounds were chosen for induced fit docking based on the docking score and glide energy obtained from GLIDE-XP docking. The compounds were docked with the protein target human aldose reductase (PDB ID: 2FZD) for checking the anti-diabetic nature. The molecular dynamics simulations were carried out for the most favorable compounds and stability has been checked during the simulations. The ethanol extract exhibits significant α-amylase and α-glucosidase inhibitory activities with an IC50 value of 38µg and 88µg dry extract respectively and well compared with standard acarbose drug.The antimicrobial activity was also carried out for various extracts (Chloroform, Ethyl acetate and Ethanol) of the same (C. intybus) was screened against four selected human pathogens. Compared to other solvent extracts, ethanol and chloroform extract shows better inhibition and their minimal inhibitory concentration (MIC) value has been calculated. Conclusion: In-silico studies and in-vitro studies reveals that C.intybus plant compounds have more potent for treating diabetes

Periplaneta americana L. a potential source of traditional medicine: chemometric analysis, in vitro and in silico study

2021 ◽  
pp. 1-17
Author(s):  
Suchismeeta Behera ◽  
Amulyaratna Behera ◽  
Suman Kumar Mekap ◽  
Chinmaya Chidananda Behera ◽  
Atul Kadam ◽  
...  
Keyword(s):  
Traditional Medicine ◽  
In Silico ◽  
Periplaneta Americana ◽  
Chemometric Analysis ◽  
Potential Source ◽  
In Silico Study

Anti-Alzheimer Chemical Constituents of Morus macroura Miq.: Chemical Profiling, In silico, and In vitro Investigations

2021 ◽  
Author(s):  
Seham S. Elhawary ◽  
Ahmed Mohamed Sayed ◽  
Marwa Yousry Issa ◽  
Hanaa S. Ebrahim ◽  
Rania Alaaeldin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
In Silico ◽  
Chemical Constituents ◽  
Bioactive Metabolites ◽  
Chemical Profiling ◽  
Potential Source

Herein, we investigated both fruits and leaves of M. macroura Miq. as a potential source of bioactive metabolites against Alzheimer's disease (AD). Chemical profiling of its extracts showed that they...

IN VITRO/IN SILICO CHARACTERIZATION OF ACTIVE AND PASSIVE STRESSES IN CARDIAC MUSCLE

2012 ◽  
Vol 10 (2) ◽  
pp. 171-188 ◽  
Author(s):  
Markus Boel ◽  
Oscar J. Abilez ◽  
Ahmed N Assar ◽  
Christopher K. Zarins ◽  
Ellen Kuhl
Keyword(s):  
Cardiac Muscle ◽  
In Silico ◽  
In Silico Characterization
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