Comprehensive computational investigation for ligand recognition and binding dynamics of SdiA: a degenerate LuxR -type receptor in Klebsiella pneumoniae.

SdiA is a LuxR-type receptor that controls the virulence of Klebsiella pneumoniae, a Gram-negative bacterium that causes various infections in humans. SdiA senses exogenous acyl-homoserine lactones (AHLs) and autoinducer-2 (AI-2), two types of quorum sensing signals produced by other bacterial species. However, the molecular details of how SdiA recognizes and binds to different ligands and how this affects its function and regulation in K. pneumoniae still need to be better understood. This study uses computational methods to explore the protein-ligand binding dynamics of SdiA with 11 AHLs and 2 AI-2 ligands. The 3D structure of SdiA was predicted through homology modeling, followed by molecular docking with AHLs and AI-2 ligands. Binding affinities were quantified using MM-GBSA, and complex stability was assessed via Molecular Dynamics (MD) simulations. Results demonstrated that SdiA in Klebsiella pneumoniae exhibits a degenerate binding nature, capable of interacting with multiple AHLs and AI-2. Specific ligands, namely C10-HSL, C8-HSL, 3-oxo-C8-HSL, and 3-oxo-C10-HSL, were found to have high binding affinities and formed critical hydrogen bonds with key amino acid residues of SdiA. This finding aligns with the observed preference of SdiA for AHLs having 8 to 10 carbon-length acyl chains and lacking hydroxyl groups. In contrast, THMF and HMF demonstrated poor binding properties. Furthermore, AI-2 exhibited a low affinity, corroborating the inference that SdiA is not the primary receptor for AI-2 in K. pneumoniae. These findings provide insights into the protein-ligand binding dynamics of SdiA and its role in quorum sensing and virulence of K. pneumoniae.

Probing the effects of streptomycin on Brassica napus germination and assessing its molecular interactions using extensive molecular dynamics (MD) simulations.

Antibiotics are chemical compounds that are used to treat and prevent disease in humans and animals. They have been used in animal feed for over 60 years and are widely used in industrial farming. Antibiotics can have negative environmental impacts, including the potential to contribute to the development of antibiotic-resistant organisms. They can enter the environment through various pathways, including the manufacturing process, the direct application of antibiotic-laden manure to fields, and through grazing animals. Antibiotics that are given to animals can be excreted from where they can enter soil and groundwater which enable their entry in plants. Streptomycin is an antibiotic that is used against a range of gram-positive and gram-negative bacteria, but its use has led to the development of antibiotic resistance in some pathogens. It has also been shown to have negative impacts on a range of plant species, including tobacco, tomato, and wheat. Although, the major effect of streptomycin on plant physiology have been studied, the molecular mechanisms at play are barely understood in plant body. In current study, we examined the impact of streptomycin on germination of Brassica napus and then using docking, MM-GBBSA and MD simulations identified key proteins that interact with streptomycin by performing rigorous computational screening of 106 different proteins. Our finding suggest that streptomycin might be interacting with acyl-CoA oxidases, protochlorophyllide reductase B and leucoanthocyanidin dioxygenase based on simulation and docking analysis.

Enhanced exopolysaccharide production by multi metal tolerant Klebsiella variicolaSMHMZ46 isolated from mines area and application in metal bioremediation / Producción mejorada de exopolisacáridos por Klebsiella variicolaSMHMZ46 tolerante a múltiples metales aislada del área de minas y aplicación en la biorremediación de metales

The current study aimed to enhance exopolysaccharide production by Klebsiella variicolaSMHMZ46 isolated from the Zawar mines area in Udaipur, Rajasthan, India, by optimizing the medium with OFAT and a central composite design. The trial including sucrose (9.5%), casein hydrolysate (3%), and NaCl (0.5%) yielded the maximum EPS production as indicated by applying the CCD-RSM biostatistical program. The composition of exopolysaccharides produced by Klebsiella variicolaSMHMZ46 culture was characterized. Growth under Pb(II), Cd(II), and Ni(II) metal amended conditions induced EPS production relative to control. TLC was used for identifying the sugar residues of EPS, in addition to determination of both total carbohydrate and protein contents. According to FT-IR analysis, EPS can interact with metal ions via their functional chemical groups, thereby supporting their bioremediation potential. The metal removal efficiency of bacteria and their produced EPS in broth individually spiked with Pb(II), Ni(II), and Cd(II) was 99.18%, 97.60%, and 98.20%, respectively, and powdered EPS from contaminated water was 85.76%, 72.40%, and 71.53%, respectively. According to FEG-SEM observations, the surface morphology of EPS becomes rough, demonstrating sharp bumps after metal binding. A FEG-SEM analysis of the structure of EPS was performed; the surface structure of EPS (with metal) was more rigid than that of control EPS (without metal). The interaction between the EPS system and Pb(II) ions was investigated using FEG-SEM coupled with energy dispersive X-ray spectra, and a strong peak of C, O, and Pb elements was observed, indicating successful Pb adsorption. These findings suggest that EPS from Klebsiella variicolaSMHMZ46 has a good metal adsorbing nature and could be a promising biosorbent for metal bioremediation of contaminated water.(AU)

Biofilm-forming plant growth-promoting rhizobacterial consortia isolated from mines and dumpsites assist green remediation of toxic metal (Ni and Pb) using Brassica juncea.

To study how biofilm-forming rhizobacteria isolated from mines and dumpsites improved the phytoremediation efficacy of B. juncea in metal-contaminated soil. Out of 91 isolates, six were chosen for research based on their tolerance to metals, and their efficient PGPR properties, and subjected to the design of a consortium. A compatibility study revealed no antagonistic interaction between rhizobacterial-consortiums. The results of the biofilm formation and FEG-SEM studies revealed that a consortium-BC8 formed a strong biofilm on the root surface of B. juncea seedlings. Based on results obtained with the phytoextraction efficiency of B. juncea in consortium-BC8 (SMHMZ46 and SMHMP23), they were identified as Klebsiella variicola and Pseudomonas otitidis, respectively, and submitted to NCBI GenBank with accession numbers MZ145092 and OK560623. This rhizobacteria is the first to be reported as assisting Ni and Pb phytoremediation by employing B. juncea. Soil inoculation with consortium-BC8 increased the amount of soluble Ni and Pb by 13.25-fold and 10.69-fold, respectively, when compared to the control. These consortiums-BC8 significantly increased vegetative growth and metal accumulation in root and shoot with a translocation-factor of 1.58 for Ni and soil to root with a bioconcentration-factor of 1.3 for Pb in B. juncea grown in individual soil contamination with 96.05 mg/kg NiCl2 and 89.63 mg/kg Pb(NO3)2, which are significantly higher than other consortium treatments and the non-inoculated control. B. juncea amendments with a biofilm-forming consortium-BC8 having TF, BCF, and BAC > 1 for Ni, whereas BCF > 1, TF, and BAC < 1 for Pb, are appropriate for green remediation of Ni and phytostabilization of Pb.

Characterizing and demonstrating the role of Klebsiella SSN1 exopolysaccharide in osmotic stress tolerance using neutron radiography.

Exopolysaccharides (EPS) are organic macromolecules naturally secreted by many microorganisms. EPS is increasingly used for agriculture and industrial purposes. This study focuses on isolate Klebsiella pneumonia SSN1, Klebsiella quasipeumonniae SGM81 isolated from rhizosphere to explore its water retention efficiency under drought conditions. Neutron Radiography was used to visualise water distribution in the sand under normal and drought conditions in the presence and absence of EPS producing bacteria. The EPS production was studied by applying Box Behnken design (BBD) under drought stress which was artificially induced by using polyethene glycol 6000 under osmotic stress condition 3.65% w/v of EPS dry weight was obtained. The relative water content (RWC) is used to calculate the amount of water present in the sand and was further studied by Neutron Radiography imaging with appropriate controls. FTIR and HPLC were also carried out for the characterisation of the extracted EPS. The sand experiments revealed that after 24 h of evaporation, the highest RWC was maintained by SSN1 at 29.7% compared to SGM81 (19.06%). SSN1 was found to release L-arabinose as the main sugar of its EPS under drought stress conditions by HPLC method. The FTIR data indicated the presence of ß-glucans and polysaccharide α-pyranose between wavenumber 700 cm-1-1500 cm-1 and 1017 cm-1-1200 cm-1 respectively. The HPLC characterization of extracted EPS from osmotic stressed cells (run 3) displayed a peak designated to L-arabinose at 10.3 retention time (RT) for 132.4 mM concentration. While from run 5 with the controlled condition indicated the presence of L-rhamnose at 7.3 RT for 87 mM concentration. Neutron radiography enables the visualisation of water distribution in the sand as well as water transport in root-soil systems in situ. SSN1 has elicited EPS production in drought conditions with a low level of nitrogen and carbon.

Enhanced exopolysaccharide production by multi metal tolerant Klebsiella variicolaSMHMZ46 isolated from mines area and application in metal bioremediation.

The current study aimed to enhance exopolysaccharide production by Klebsiella variicolaSMHMZ46 isolated from the Zawar mines area in Udaipur, Rajasthan, India, by optimizing the medium with OFAT and a central composite design. The trial including sucrose (9.5%), casein hydrolysate (3%), and NaCl (0.5%) yielded the maximum EPS production as indicated by applying the CCD-RSM biostatistical program. The composition of exopolysaccharides produced by Klebsiella variicolaSMHMZ46 culture was characterized. Growth under Pb(II), Cd(II), and Ni(II) metal amended conditions induced EPS production relative to control. TLC was used for identifying the sugar residues of EPS, in addition to determination of both total carbohydrate and protein contents. According to FT-IR analysis, EPS can interact with metal ions via their functional chemical groups, thereby supporting their bioremediation potential. The metal removal efficiency of bacteria and their produced EPS in broth individually spiked with Pb(II), Ni(II), and Cd(II) was 99.18%, 97.60%, and 98.20%, respectively, and powdered EPS from contaminated water was 85.76%, 72.40%, and 71.53%, respectively. According to FEG-SEM observations, the surface morphology of EPS becomes rough, demonstrating sharp bumps after metal binding. A FEG-SEM analysis of the structure of EPS was performed; the surface structure of EPS (with metal) was more rigid than that of control EPS (without metal). The interaction between the EPS system and Pb(II) ions was investigated using FEG-SEM coupled with energy dispersive X-ray spectra, and a strong peak of C, O, and Pb elements was observed, indicating successful Pb adsorption. These findings suggest that EPS from Klebsiella variicolaSMHMZ46 has a good metal adsorbing nature and could be a promising biosorbent for metal bioremediation of contaminated water.

A clash of quorum sensing vs quorum sensing inhibitors: an overview and risk of resistance.

Indiscriminate use of antibiotics to treat microbial pathogens has caused emergence of multiple drug resistant strains. Most infectious diseases are caused by microbes that are capable of intercommunication using signaling molecules, which is known as quorum sensing (QS). Such pathogens express their pathogenicity through various QS-regulated virulence factors. Interference of QS could lead to decisive results in controlling such pathogenicity. Hence, QS inhibition has become an attractive new approach for the development of novel drugs. Many quorum sensing inhibitors (QSIs) of diverse origins have been reported. It is imperative that more such anti-QS compounds be found and studied, as they have significant effect on microbial pathogenicity. This review attempts to give a brief account of QS mechanism, its inhibition and describes some compounds with anti-QS potential. Also discussed is the possibility of emergence of quorum sensing resistance.

Rapid method for detection, quantification and measuring microbial degradation of pesticide-thiram using high performance thin layer chromatography (HPTLC).

Thiram (tetramethylthiuramdisulfide) or thiram sulphide is a dithiocarbamate group of non-systemic group of fungicide which are applied for seed treatment, control of the crop pests, to repel animals, etc. Moreover, thiram has also been responsible to cause moderate skin sensitivity and eye irritation. Higher exposure to thiram might also lead to developmental damages to newborn and neurotoxic effects to non-target organisms. Advancing to prevent such toxic effects and prevention of soil fertility from thiram and thiram-like chemicals is indispensable. The analytical High-Performance Thin-Layer Chromatography (HPTLC) is a simple, quick and a reliable method was proposed and validated for the detection and quantification of various small molecules for many years. This manuscript represents the solution to use microbes to degrade the thiram present in the soil and for that, HPTLC based method to study thiram degradation by Pseudomonas has been designed. Herein, a HPTLC protocol formalised to reveal the detection and quantification of thiram within the range of 100 to 700 ng/spot on TLC plate. The same concentration was then used for calculating percent microbial degradation of thiram from the culture broth. To perform the microbial degradation of thiram, Pseudomonas otitidis strain TD-8 and Pseudomonas stutzeri strain TD-18 were taken as thiram degrader microbial strain. The efficacy of TD-8 to degrade thiram was identified to be 81 and 99% when grown in presence of thiram for 4 days and 8 days, respectively, while TD-18 strain's efficacy to degrade thiram was found to be 57% and 99% when grown in presence of thiram for 4 days and 8 days, respectively.

Rhizosphere microbiome analysis of healthy and infected cumin (Cuminum cyminum L.) varieties from Gujarat, India.

Cumin (Cuminum cyminum L.; Jeera) is a popular herbal seed spice used in culinary preparation in India. Gujarat and Rajasthan are the largest producer states of cumin seeds from India, while India is also the largest supplier and exporter of cumin across the globe. However, production of cumin is suffering from loss of crop production due to the plant pathogen infections, especially from Fusarium oxysporium sp. Rhizomicrobiome is the key modulator of plant health, revitalizing nutrients and disease response against plant pathogens. The secretion of different metabolites such as root exudates plays an important role in host plant rhizosphere microbial interactions influencing the plant health, growth and development, nutrient acquisition, and disease resistance. Therefore, in this research study, we have examined the microbial diversity from the healthy and fungal infected rhizosphere samples of the three different Gujarat Cumin (GC-2, GC-3, and GC-4) varieties using 16S ribosomal RNA (rRNA) gene sequencing on Ion Torrent S5 sequencing platform. The findings revealed the major dominant family represented by Bacillaceae, Solibacteraceae, Nostocaceae, Paenibacillaceae, Scytonemataceae, and Halothiobacillaceae, while at genera level of taxonomic abundance were represented by Bacillus, Candidatus Solibacter, Synechococcus, Nostoc, Anabaena, and Oscillatoria. The research findings should enhance our understanding of healthy and infected plant rhizosphere microbiome for better crop productivity, disease resistance and management of the crop varieties against plant pathogens.

Interactive bioinformatics analysis for the screening of hub genes and molecular docking of phytochemicals present in kitchen spices to inhibit CDK1 in cervical cancer.

Cervical cancer (CC) is the world's fourth most prevalent cancer among women. The mortality rate of cervical cancer increases each year due to a lack of early diagnosis. Our study aims to find potential genes linked to cervical cancer and validate the findings using docking analysis. The microarray datasets (GSE6791, GSE7803, GSE9750, GSE39001, GSE52903, GSE63514, and GSE75132) were downloaded from the GEO (Gene Expression Omnibus) database. A total of 1160 Differentially Expressed Genes (DEGs) were discovered using the R statistical language, including 825 up-regulated and 335 down-regulated genes. STRING, which predicts the potential interaction between genes at the protein level, was used to build the PPI network of these DEGs. Moreover, hub gene expression analysis was carried out by CytoHubba plugin Cytoscape. CDK1 was considered for subsequent molecular docking because of its frequent appearance throughout the analysis. CDK1 was docked with the 399 phytochemicals of Indian kitchen spices. The top three compounds namely, Vicenin 2, 2-O,3-O,4-O,6-O-Tetragalloyl-d-glucopyranose and Pentagalloylglucose, were chosen based on their docking scores and their interactions with the key amino acids present in the ATP binding pocket, like the positive control Dinaciclib. In conclusion, the findings of this study may lead to new insights on CC diagnosis, aetiology, and treatment options. In the future, it may be possible to develop particular diagnostics and therapies for CC by identifying hub genes and studying overexpressed proteins as therapeutic targets.

Perceiving SARS-CoV-2 Mpro and PLpro dual inhibitors from pool of recognized antiviral compounds of endophytic microbes: an in silico simulation study.

Coronavirus disease 2019 (COVID-19) persists and shook the global population where the endgame to this pandemic is brought on by developing vaccines in record-breaking time. Nevertheless, these vaccines are far from perfect where their efficiency ranges from 65 to 90%; therefore, vaccines are not the one only solution to overcome this situation, and apart from administration of vaccines, the scientific community is at quest for finding alternative solutions to incumber SARS-CoV-2 infection. In this study, our research group is keen on identifying a bioactive molecule that is independent in its mode of action from existing vaccines which can potentially target the SARS-CoV-2 virus replicative efficacy. Papain-like protease (PLpro) and main protease (Mpro) are the most lucrative targets of COVIDs against which the drugs can be developed, as these proteases play a vital role in the replication and development of viral particles. Researchers have modelled a compound such as GRL0617 and X77 as an inhibitor of Mpro and PLpro, respectively, but use of these compounds has several limitations on hosts like toxicity and solubility. Under the current study by deploying rigorous computational assessments, pool of microbial secondary metabolites was screened and handpicked to search a structural or functional analogue of GRL0617 and X77, with an idea to identify a compound that can serve as dual inhibitor for both PLpro and Mpro. From the manually curated database of known antiviral compounds from fungal origin, we found cytonic acids A and B to potentially serve as dual inhibitor of PLpro and Mpro.

Proposing a fungal metabolite-flaviolin as a potential inhibitor of 3CLpro of novel coronavirus SARS-CoV-2 identified using docking and molecular dynamics.

The novel SARS-CoV-2 is the etiological agent causing the Coronavirus disease 2019 (COVID-19), which continues to become an inevitable pandemic outbreak. Over a short span of time, the structures of therapeutic target proteins for SARS-CoV-2 were identified based on the homology modelled structure of similar virus, SARS-CoV that transmitted rapidly in 2003. Since the outset of the disease, the research community has been looking for a potential drug lead. Out of all the known resolved structures related to SARS-CoV-2; 3-chymotrypsin (3 C) like protease (3CLpro) is considered as an attractive anti-viral drug compound on the grounds of its role in viral replication and probable non-interactive competency to bind to any viral host protein. To the best of our knowledge, till date only one compound has been identified and tested in-vitro as a potent inhibitor of 3CLpro protein, addressed as N3 (PubChem Compound CID: 6323191) and is known to bind irreversibly to 3CLpro suppressing its activity. Using computational approach, we intend to identify a probable natural fungal metabolite to interact and inhibit 3CLpro. Here after performing docking and molecular dynamics of various small molecules derived as a secondary metabolite from fungi, we propose Flaviolin as potent inhibitor of 3CLpro of novel Coronavirus SARS-CoV-2.Communicated by Ramaswamy H. Sarma.

Curse of La Corona: unravelling the scientific and psychological conundrums of the 21st century pandemic.

Microbes possess a tremendous potential to interact with their surroundings and have continued to shape the future of all life forms existing on earth. Of all the groups of microbes, viruses are the most nefarious creatures which cannot be solely classified as living or non-living but still pose the greatest threats to the biosphere. Viruses are minuscule, diverse and are probably the only entities that exhibit non-mutualistic association with other lifeforms while retaining their ability to infect and hijack any of the existing living being on the planet. The latest global devastation, caused by novel SARS-CoV-2, is unparalleled in the last century. This review encompasses the mysterious origin of this virus by tracking its lineage, which may help to decode the conundrum of SARS-CoV-2 and shed more light on its epidemiology. The implications and the challenge posed by this virus to the scientific community to the medical community and the economy at large are reflected. Also discussed is the paradigm shift brought upon by the COVID-19 pandemic on the human psyche and their behaviour.

Meticulous assessment of natural compounds from NPASS database for identifying analogue of GRL0617, the only known inhibitor for SARS-CoV2 papain-like protease (PLpro) using rigorous computational workflow.

The latest global outbreak of 2019 respiratory coronavirus disease (COVID-19) is triggered by the inception of novel coronavirus SARS-CoV2. If recent events are of any indicators of the epidemics of past, it is undeniable to state a fact that the SARS-CoV2 viral infection is highly transmissible with respect to its previously related SARS-CoV's. Papain-like protease (PLpro) is an enzyme that is required by the virus itself for replicating into the host system; and it does so by processing its polyproteins into a functional replicase complex. PLpro is also known for downregulating the genes responsible for producing interferons, an essential family of molecules produced in response to viral infection, thus making this protein an indispensable drug target. In this study, PLpro inhibitors were identified through high throughput structure-based virtual screening approach from NPASS natural product library possessing ~ 35,000 compounds. Top five hits were scrutinised based on structural aromaticity and ability to interact with a key active site residue of PLpro, Tyr268. For second level of screening, the MM-GBSA End-Point Binding Free Energy Calculation of the docked complexes was performed, which identified Caesalpiniaphenol A as the best hit. Caesalpiniaphenol A not only possess a double ring aromatic moiety but also has lowest minimum binding energy, which is at par with the control GRL0617, the only known inhibitor of SARS-CoV2 PLpro. Details of the Molecular Dynamics (MD) simulation and ADMET analysis helped to conclusively determine Caesalpiniaphenol A as potentially an inhibitor of SARS-CoV2 PLpro.

Identifying structural-functional analogue of GRL0617, the only well-established inhibitor for papain-like protease (PLpro) of SARS-CoV2 from the pool of fungal metabolites using docking and molecular dynamics simulation.

The non-structural protein (nsp)-3 of SARS-CoV2 coronavirus is sought to be an essential target protein which is also named as papain-like protease (PLpro). This protease cleaves the viral polyprotein, but importantly in human host it also removes ubiquitin-like interferon-stimulated gene 15 protein (ISG15) from interferon responsive factor 3 (IRF3) protein which ultimately downregulates the production of type I interferon leading to weakening of immune response. GRL0617 is the most potent known inhibitor for PLpro that was initially developed for SARS outbreak of 2003. The PLpro of SARS-CoV and CoV2 share 83% sequence identity but interestingly have several identical conserved amino acids that suggests GRL0617 to be an effective inhibitor for PLpro of SARS-CoV2. GRL0617 is a naphthalene-based molecule and interacts with Tyr268 of SARS-CoV2-PLpro (and Tyr269 of SARS-CoV-PLpro). To identify PLpro inhibitors, we prepared a library of secondary metabolites from fungi with aromatic nature and docked them with PLpro of SARS-CoV and SARS-CoV2. We found six hits which interacts with Tyr268 of SARS-CoV2-PLpro (and Tyr269 of SARS-CoV-PLpro). More surprisingly the top hit, Fonsecin, has naphthalene moiety in its structure, which recruits Tyr268 of SARS-CoV2-PLpro (and Tyr269 of SARS-CoV-PLpro) and has binding energy at par with control (GRL0617). Molecular dynamics (MD) simulation showed Fonsecin to interact with Tyr268 of SARS-CoV2-PLpro more efficiently than control (GRL0617) and interacting with a greater number of amino acids in the binding cleft of PLpro.

An Anecdote on Prospective Protein Targets for Developing Novel Plant Growth Regulators.

Phytohormones are the main regulatory molecules of core signalling networks associated with plant life cycle regulation. Manipulation of hormone signalling cascade enables the control over physiological traits of plant, which has major applications in field of agriculture and food sustainability. Hence, stable analogues of these hormones are long sought after and many of them are currently known, but the quest for more effective, stable and economically viable analogues is still going on. This search has been further strengthened by the identification of the components of signalling cascade such as receptors, downstream cascade members and transcription factors. Furthermore, many proteins of phytohormone cascades are available in crystallized forms. Such crystallized structures can provide the basis for identification of novel interacting compounds using in silico approach. Plenty of computational tools and bioinformatics software are now available that can aid in this process. Here, the metadata of all the major phytohormone signalling cascades are presented along with discussion on major protein-ligand interactions and protein components that may act as a potential target for manipulation of phytohormone signalling cascade. Furthermore, structural aspects of phytohormones and their known analogues are also discussed that can provide the basis for the synthesis of novel analogues.

Repurposing the antibacterial drugs for inhibition of SARS-CoV2-PLpro using molecular docking, MD simulation and binding energy calculation.

Papain-like protease (nsp-3; non-structural protein) of novel corona virus is an ideal target for developing drugs as it plays multiple important functions for viral growth and replication. For instance, role of nsp-3 has been recognized in cleavage of viral polyprotein; furthermore, in infected host it weakens the immune system via downregulating the production of type I interferon. This downregulation is promoted by removal of ubiquitin-like interferon-stimulated gene 15 protein (ISG15) from interferon-responsive factor 3 (IRF3) protein. Among known inhibitors of SARS-CoV-PLpro GRL0617 is by far the most effective inhibitor. As PLpro of SARS-CoV2 is having more than 80% similarity with SARS-CoV-PLpro, GRL0617 is reported to be effective even against SARS-CoV2. Owing to this similarity, certain key amino acids remain the same/conserved in both proteins. Among conserved amino acids Tyr268 for SARS-CoV2 and Tyr269 for SARS-CoV produce important hydrophobic interactions with aromatic rings of GRL0617. Here, in this study antibacterial compounds were collected from ZINC database, and they were filtered to select compounds that are having similar structural features as GRL0617. This filtered library of compound was then docked with SARS-CoV and CoV2-PLpro. Five hits were noted that were able to interact with Tyr268 (SARS-CoV2) and Tyr269 (SARS-CoV). Further, best hit 2-(2-((benzofuran-2-carboxamido)methyl)-5-methoxy-1H-indol-1-yl)acetic acid (ZINC44459905) was studied using molecular dynamic simulation where stability of protein-ligand complex as well as stability of produced interactions was noted.

Articulating the exuberant intricacies of bacterial exopolysaccharides to purge environmental pollutants.

Microbial exopolysaccharide (EPS) is composed of a mixture of macromolecules such as proteins, polysaccharides, humic-like compounds, and nucleic acids, which encase microbial cells in a three-dimensional matrix. The literature shows that the EPS possess significant properties such as renewable, biodegradable, eco-friendly, non-toxic, and economically valued product, representing it as a green alternative to the synthetic polymer. The cost-effective and green synthesis of the EPS must be encouraged by using agro-waste as a raw material. The main objective of the manuscript is to provide a comprehensive update on the various aspects pertaining to EPS, including the economic aspects of EPS production, provide an insight into the latest tools and techniques used for detailed structural EPS characterization along with updates in the integration of CRISPR/Cas9 technology for engineering the modification in EPS production, the role of newly discovered EPR3 as a signalling molecule in plant growth-promoting properties (PGP) or agricultural microbiology. Furthermore, the EPS achieved prospective interest prevailing potential environmental issues which can be subject to EPS treatment including, landfill leachate treatment, decolourization of dye from the effluent or waste generated by an industry, removal of radionuclides, heavy metals and toxic compounds from the various environments (aquatic and terrestrial), industry effluents, waste waters etc. are comprehensively discussed.

Exemplifying the next generation of antibiotic susceptibility intensifiers of phytochemicals by LasR-mediated quorum sensing inhibition.

There persists a constant threat from multidrug resistance being acquired by all human pathogens that challenges the well-being of humans. This phenomenon is predominantly led by Pseudomonas aeruginosa which is already resistant to the current generations of antibiotic by altering its metabolic pathways to survive. Specifically for this microbe the phenomenon of quorum sensing (QS) plays a crucial role in acquiring virulence and pathogenicity. QS is simply the cross talk between the bacterial community driven by signals that bind to receptors, enabling the entire bacterial microcosm to function as a single unit which has led to control P. aeruginosa cumbersome even in presence of antibiotics. Inhibition of QS can, therefore, be of a significant importance to curb such virulent and pathogenic strains of P. aeruginosa. Natural compounds are well known for their antimicrobial properties, of which, information on their mode of action is scarce. There can be many antimicrobial phytochemicals that act by hindering QS-pathways. The rationale of the current study is to identify such natural compounds that can inhibit QS in P. aeruginosa driven by LasR, PhzR, and RhlR dependent pathways. To achieve this rationale, in silico studies were first performed to identify such natural compounds which were then validated by in vitro experiments. Gingerol and Curcumin were identified as QS-antagonists (QSA) which could further suppress the production of biofilm, EPS, pyocyanin, and rhamnolipid along with improving the susceptibility to antibiotics.

Breaking bad: Better call gingerol for improving antibiotic susceptibility of Pseudomonas aeruginosa by inhibiting multiple quorum sensing pathways.

Pseudomonas aeruginosa is recognized as a bacterium with many bullets in its armoury and the Achilles heel of the bacterium is that it exudes several pathways that lead to pathogenicity thereby making the application of the strain cautious since the bacterium is known as a 'superbug' ergo, being resistant to multiple antibiotics. The mechanisms of pathogenicity are mainly driven by quorum sensing (QS), a phenomenon that works on cell-cell communication through classical ligand-receptor interactions. QS-mediated pathways enable control of this organism impossible even with the use of antibiotics. Henceforth, interfering with the QS pathways serves as a new mode of action for futuristic antibiotics to decrease the distress of this microbe. We propose gingerol to interfere with various QS-receptors of P. aeruginosa (LasR, PhzR and RhlR) which were deduced using in silico approach and validated in vitro by assessing its impact on EPS, biofilm, pyocyanin and rhamnolipid of the microbe. Further, gingerol was found to increase the antibacterial potency of the antibiotic when applied in integration with ciprofloxacin. The findings provide an insight about preferring the integrated approach of using QS-inhibitors (QSI) in tandem with antibiotics for holistic strategy in fight against the phenomenon of antibiotic resistance acquired by microbes.