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1.
Diagn Microbiol Infect Dis ; 109(1): 116212, 2024 May.
Article in English | MEDLINE | ID: mdl-38387214

ABSTRACT

Pseudomonas aeruginosa, one of the most notorious organisms, causes fatal diseases like-, meningitis, pneumonia as well as worsens the prognosis of cystic fibrosis patients. It is also multi-drug resistant and resists a wide range of antibiotics. Attempts have been made to reduce its virulence/pathogenic potential using a number of organic compounds. For this purpose, the Quorum sensing (QS) system of P. aeruginosa was targeted, which regulates its virulence. Pseudomonas Quinolone System (PQS), one of the four quorum sensing systems, producing pyocyanin pigment was chosen. 2-heptyl-3-hydroxy-4-quinolone (HHQ) is a ligand which binds to PQS protein is responsible for pyocyanin pigment production. Attempts were made to find a compound analogous to HHQ which could bind to PQS active site and inhibit the pigment formation. In-silico analysis was performed to estimate possible interactions and to find/predict the possible PQS inhibitors.


Subject(s)
Pseudomonas Infections , Quinolones , Humans , Quorum Sensing/physiology , Pseudomonas aeruginosa/metabolism , Pseudomonas/metabolism , Pyocyanine/metabolism , Quinolones/pharmacology , Pseudomonas Infections/drug therapy , Bacterial Proteins/metabolism
2.
Curr Diabetes Rev ; 2023 Nov 06.
Article in English | MEDLINE | ID: mdl-37933216

ABSTRACT

Bioactive compounds found in various natural sources, such as fruits, vegetables, and herbs, have been studied for their potential benefits in managing obesity and diabetes. These compounds include polyphenols, flavonoids, other antioxidants, fiber, and certain fatty acids. Studies have found that these compounds may improve insulin sensitivity, regulate blood sugar levels, and promote weight loss. However, the effects of these compounds can vary depending on the type and amount consumed, as well as individual factors, such as genetics and lifestyle. Nutraceutical substances have multifaceted therapeutic advantages, and they have been reported to have disease-prevention and health-promoting properties. Several clinically used nutraceuticals have been shown to target the pathogenesis of diabetes mellitus, obesity, and metabolic syndrome and their complications and modulate various clinical outcomes favorably. This review aims to highlight and comment on some of the most prominent natural components used as antidiabetics and in managing obesity.

3.
Mar Pollut Bull ; 177: 113509, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35290835

ABSTRACT

Plastic comprises of variety of polymers and has many applications, but the waste generated by plastic pose threat to environment and marine life. Plastic can be classified into two types: thermoplastics and thermosetting and are divided into 7 different categories: (Polyethylene Terephthalate [PETE], High-Density Polyethylene [HDPE], Polyvinyl Chloride [PVC], Low-Density Polyethylene [LDPE], Polypropylene [PP], Polystyrene or Styrofoam [PS] & Polycarbonate or ABS [others]). To curb the deleterious effects of plastic waste various methods have been devised and utilized that include chemical, physical and biological treatments. One of the aspects primarily focused by the researchers is the phenomenon of biodegradation and there are many microorganisms (bacteria) that have the ability to carry out this particular process. These bacteria assist biodegradation by production of several enzymes like PETases and MHETases. There are few microorganisms that have been listed which cannot be applied for industrial use due to its low biodegradation capacity. To overcome this problem, PHA is one of the alternatives to replace the synthetic plastic due to its high degrading capacity.


Subject(s)
Plastics , Polymers , Biodegradation, Environmental , Plastics/chemistry , Polyethylene , Polypropylenes
4.
J Biomol Struct Dyn ; 40(1): 348-360, 2022 Jan.
Article in English | MEDLINE | ID: mdl-32875950

ABSTRACT

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.


Subject(s)
COVID-19 , Molecular Dynamics Simulation , Fungi , Humans , Molecular Docking Simulation , Naphthoquinones , Protease Inhibitors , SARS-CoV-2
5.
Mol Divers ; 26(1): 555-568, 2022 Feb.
Article in English | MEDLINE | ID: mdl-33392967

ABSTRACT

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.


Subject(s)
COVID-19 , Pandemics , COVID-19/epidemiology , Humans , SARS-CoV-2
6.
Mol Divers ; 26(1): 389-407, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34008129

ABSTRACT

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.


Subject(s)
COVID-19 Drug Treatment , Papain , Aniline Compounds , Benzamides , Humans , Naphthalenes , Peptide Hydrolases , RNA, Viral , SARS-CoV-2 , Workflow
7.
Mol Divers ; 26(1): 309-329, 2022 Feb.
Article in English | MEDLINE | ID: mdl-33825097

ABSTRACT

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.


Subject(s)
COVID-19 Drug Treatment , Molecular Dynamics Simulation , Aniline Compounds , Benzamides , Fungi/metabolism , Humans , Molecular Docking Simulation , Naphthalenes , Papain/chemistry , Papain/metabolism , Peptide Hydrolases/metabolism , RNA, Viral , SARS-CoV-2
8.
Heliyon ; 7(11): e08446, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34877428

ABSTRACT

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.

9.
Sci Rep ; 11(1): 22421, 2021 11 17.
Article in English | MEDLINE | ID: mdl-34789810

ABSTRACT

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.


Subject(s)
Anti-Bacterial Agents/pharmacology , Bacterial Proteins/metabolism , Catechols/pharmacology , Curcumin/pharmacology , Fatty Alcohols/pharmacology , Phytochemicals/pharmacology , Pseudomonas Infections/metabolism , Pseudomonas aeruginosa/drug effects , Quorum Sensing/drug effects , Signal Transduction/drug effects , Trans-Activators/metabolism , Biofilms/drug effects , Glycolipids/metabolism , Microbial Sensitivity Tests , Molecular Dynamics Simulation , Pseudomonas Infections/microbiology , Pseudomonas aeruginosa/metabolism , Pseudomonas aeruginosa/pathogenicity , Pyocyanine/metabolism , Virulence/drug effects
10.
Microbiol Res ; 252: 126863, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34530246

ABSTRACT

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.


Subject(s)
Catechols , Drug Resistance, Bacterial , Fatty Alcohols , Pseudomonas aeruginosa , Quorum Sensing , Anti-Bacterial Agents/pharmacology , Catechols/pharmacology , Drug Resistance, Bacterial/drug effects , Fatty Alcohols/pharmacology , Pseudomonas aeruginosa/drug effects , Quorum Sensing/drug effects
11.
Drug Dev Ind Pharm ; 47(5): 699-710, 2021 May.
Article in English | MEDLINE | ID: mdl-34038246

ABSTRACT

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2 or COVID-19), outbreak was first reported in December 2019 in the Wuhan, China. COVID-19 managed to spread worldwide and so far more than 9.1 million cases and more than 4.7 lakh death has been reported globally. Children, pregnant women, elderly population, immunocompromised patients, and patients with conditions like asthma, diabetes, etc. are highly vulnerable to COVID infection. Currently, there is no treatment available for COVID-19 infection. Traditional medicinal plants have provided bioactive molecules in the past that are efficiently used during conditions like cancer, malaria, microbial infections, immune-compromised states, etc. AYUSH India has recommended the use of Curcuma longa, Allium sativum, Ocimum tenuiflorum, and Withania somnifera for immune-boosting during SARS-CoV-2 infection. In the present study, we investigated the potential of 63-major bioactive molecules of these plants against SARS-CoV-2 main protease (Mpro) through docking studies and compared the results with known inhibitor 11a. Our results proposed cuscohygrine, γ-Glutamyl-S-allylcysteine, anahygrine, and S-allylcystein as the potent inhibitors against Mpro identified using molecular docking and molecular simulation dynamics. Interestingly, these molecules are from A. sativum, and W. somnifera, which are known for their antimicrobial and immunomodulatory potential. None of the proposed molecules have earlier been reported as antiviral molecules. Our results predict very strong potential of these four-molecules against SARS-CoV-2 Mpro, especially γ-glutamyl-S-allylcysteine, as all four form hydrogen bonding with Glu166 that is a crucial residue for the formation of the biologically active dimeric form of Mpro. Therefore, we strongly recommend further research on these biomolecules against SARS-CoV-2.


Subject(s)
COVID-19 , SARS-CoV-2 , Aged , Antiviral Agents , Child , China , Dipeptides , Female , Humans , Molecular Docking Simulation , Molecular Dynamics Simulation , Peptide Hydrolases , Pregnancy , Protease Inhibitors
12.
Mol Biotechnol ; 63(8): 676-685, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34021472

ABSTRACT

The flexibility of microbes to undergo or adapt to the changes in their physiology and genotypical traits has enabled the microbes acquiring resistance to latest or recently discovered drugs which have consequently led to the menace of multidrug resistance (MDR). There is a surge in the discovery of novel antibiotics to counter the rising MDR phenomena, and in such a quest, for investigating an efficient alternative mechanism or compound to combat MDR, Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) has piqued the interests of the researchers across the globe. CRISPR-Cas9 technology is a genome-editing tool with successful widespread applications in cell lines, plants, animals, and even in human clinical trials, and it is seriously being considered as a potential candidate for countering MDR. This review encompasses the broad scope of CRISPR-Cas9 along with its various variations, underlying principles, mechanisms, as well as applications. Furthermore, the implications of recent advancements in various disciplines are highlighted to enhance the applicability of this technique. Consequently, its research gaps and challenges are also identified so that they can be addressed in the possible future thereby further expanding the lore of CRISPR-Cas9 technique.


Subject(s)
CRISPR-Cas Systems , Drug Resistance, Multiple/genetics , Animals , Drug Delivery Systems , Gene Editing , Genes, MDR , Humans
13.
Sci Rep ; 11(1): 3189, 2021 02 04.
Article in English | MEDLINE | ID: mdl-33542436

ABSTRACT

It is the acquisition of unique traits that adds to the enigma of microbial capabilities to carry out extraordinary processes. One such ecosystem is the soil exposed to radionuclides, in the vicinity of atomic power stations. With the aim to study thorium (Th) tolerance in the indigenous bacteria of such soil, the bacteria were isolated and screened for maximum thorium tolerance. Out of all, only one strain AM3, found to tolerate extraordinary levels of Th (1500 mg L-1), was identified to be belonging to genus Providencia and showed maximum genetic similarity with the type strain P. vermicola OP1T. This is the first report suggesting any bacteria to tolerate such high Th and we propose to term such microbes as 'thoriotolerant'. The medium composition for cultivating AM3 was optimized using response surface methodology (RSM) which also led to an improvement in its Th-tolerance capabilities by 23%. AM3 was found to be a good producer of EPS and hence one component study was also employed for its optimization. Moreover, the EPS produced by the strain showed interaction with Th, which was deduced by Fourier Transform Infrared (FTIR) spectroscopy.

14.
Mol Biol Rep ; 47(10): 8113-8131, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32990905

ABSTRACT

Peptide Nucleic Acid (PNA) serves as an artificial functional analog of DNA. Being immune to enzymatic degradation and possessing strong affinity towards DNA and RNA, it is an ideal candidate for many medical and biotechnological applications that are of antisense and antigene in nature. PNAs are anticipated to have its application in DNA and RNA detection as well as quantification, to serve as antibacterial and antiviral agents, and silencing gene for developing anticancer strategies. Although, their restricted entry in both eukaryotic and prokaryotic cells limit their applications. In addition, aggregation of PNA in storage containers reduces the quality and quantity of functional PNA that makes it inadequate for their mass production and storage. To overcome these limitations, researchers have modified PNA either by the addition of diverse functional groups at various loci on its backbone, or by synthesizing chimeras with other moieties associated with various delivery agents that aids their entry into the cell. Here, this review article summarizes few of the structural modifications that are performed with PNA, methods used to improve their cellular uptake and shedding light on the applications of PNA in various prospects in biological sciences.


Subject(s)
DNA/analysis , Peptide Nucleic Acids/chemistry , RNA/analysis , DNA/chemistry , RNA/chemistry
15.
Biophys Chem ; 264: 106425, 2020 09.
Article in English | MEDLINE | ID: mdl-32663708

ABSTRACT

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 SARS-CoV transmission of 2003. Since the onset 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, Main protease (Mpro) is considered an attractive anti-viral drug target 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-vivo as a potent inhibitor of Mpro protein, addressed as N3 (PubChem Compound CID: 6323191) and is known to bind irreversibly to Mpro suppressing its activity. Using computational approach, we intend to identify a probable natural fungal metabolite to interact and inhibit Mpro. After screening various small molecules for molecular docking and dynamics simulation, we propose Pyranonigrin A, a secondary fungal metabolite to possess potent inhibitory potential against the Main protease (Mpro) expressed in SARS-CoV-2 virus.


Subject(s)
Antiviral Agents/chemistry , Betacoronavirus/enzymology , Protease Inhibitors/chemistry , Pyrones/chemistry , Pyrroles/chemistry , Viral Nonstructural Proteins/antagonists & inhibitors , Betacoronavirus/pathogenicity , Binding Sites , Coronavirus 3C Proteases , Crystallography, X-Ray , Cysteine Endopeptidases/chemistry , Cysteine Endopeptidases/genetics , Cysteine Endopeptidases/metabolism , Drug Discovery , Gene Expression , Hydrogen Bonding , Molecular Docking Simulation , Molecular Dynamics Simulation , Protein Binding , Protein Conformation, alpha-Helical , Protein Conformation, beta-Strand , Protein Interaction Domains and Motifs , SARS-CoV-2 , Sequence Homology, Amino Acid , Thermodynamics , Viral Nonstructural Proteins/chemistry , Viral Nonstructural Proteins/genetics , Viral Nonstructural Proteins/metabolism
16.
Microbiol Res ; 238: 126526, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32603934

ABSTRACT

The current study depicts the isolation of luminescent bacteria from fish and squid samples that were collected from Veraval fish harbour. From Indian mackerel, total 14 and from squid, total 23 bioluminescent bacteria were isolated using luminescence agar medium. Two bioluminescent bacteria with highest relative luminescence intensity PBR1 and PBL1 were selected. These two isolates were subjected to detailed biochemical characterization and were tested positive for 5 out of 13 biochemical tests. Furthermore, both PBR1 and PBL1 were able to ferment cellobiose, dextrose, fructose, galactose, maltose, mannose, sucrose and trehalose with acid production. Based on 16S rRNA partial gene sequence analysis, PBR1 was identified as Vibrio alginolyticus and PBL1 as V. rotiferianus. Antibiotic susceptibility test using paper-disc method showed that PBR1 and PBL1 were sensitive to chloramphenicol, ciprofloxacin, co-trimoxazole, gatifloxacin, levofloxacin, linezolid ad roxithromycin out of 18 antibiotics tested. Moreover, both strains were evaluated for their exopolysachharide (EPS) producing ability where PBR1 and PBL1 were able to yield 1.34 g% (w/v) and 2.45 g% (w/v) EPS respectively from 5 g% (v/v) sucrose concentration. Heavy metal toxicity assessment was carried out using agar well diffusion method with eight heavy metals and both the strains were sensitive to As(III), Cd(II), Ce(II), Cr(III), Cu(II), Hg(II) and while they showed resistance to Pb(II) and Sr(II). Based on these results, a study was conducted to demonstrate bio-removal of Pb and Sr by EPS of PBR1 and PBL1. Fourier transform infrared (FTIR) spectra revealed the functional groups of EPS involved in interaction with the heavy metals. Owing to the sensitivity for the remaining heavy metals, these bioluminescent bacteria can be used further for the development of luminescence-based biosensor.


Subject(s)
Aquatic Organisms/microbiology , Metals, Heavy/chemistry , Polysaccharides, Bacterial/chemistry , Vibrio alginolyticus/drug effects , Vibrio/drug effects , Animals , Anti-Bacterial Agents/pharmacology , Biodegradation, Environmental , DNA, Bacterial , Luminescence , Luminescent Measurements , Microbial Sensitivity Tests , Molecular Typing , Phylogeny , RNA, Ribosomal, 16S/genetics , Spectroscopy, Fourier Transform Infrared , Vibrio/classification , Vibrio/isolation & purification , Vibrio alginolyticus/classification , Vibrio alginolyticus/isolation & purification
17.
Nat Commun ; 11(1): 3228, 2020 06 26.
Article in English | MEDLINE | ID: mdl-32591529

ABSTRACT

Plasmodium falciparum (Pf) relies solely on the salvage pathway for its purine nucleotide requirements, making this pathway indispensable to the parasite. Purine nucleotide levels are regulated by anabolic processes and by nucleotidases that hydrolyse these metabolites into nucleosides. Certain apicomplexan parasites, including Pf, have an IMP-specific-nucleotidase 1 (ISN1). Here we show, by comprehensive substrate screening, that PfISN1 catalyzes the dephosphorylation of inosine monophosphate (IMP) and is allosterically activated by ATP. Crystal structures of tetrameric PfISN1 reveal complex rearrangements of domain organization tightly associated with catalysis. Immunofluorescence microscopy and expression of GFP-fused protein indicate cytosolic localization of PfISN1 and expression in asexual and gametocyte stages of the parasite. With earlier evidence on isn1 upregulation in female gametocytes, the structures reported in this study may contribute to initiate the design for possible transmission-blocking agents.


Subject(s)
5'-Nucleotidase/chemistry , 5'-Nucleotidase/metabolism , Biocatalysis , Plasmodium falciparum/enzymology , Adenosine Triphosphate/metabolism , Animals , Apoproteins/metabolism , Binding Sites , Hydrogen-Ion Concentration , Kinetics , Magnesium/metabolism , Mice, Inbred BALB C , Models, Molecular , Mutant Proteins/chemistry , Protein Domains , Protein Structure, Secondary , Protein Transport , Protozoan Proteins/chemistry , Protozoan Proteins/metabolism , Substrate Specificity
18.
Bioorg Chem ; 99: 103823, 2020 06.
Article in English | MEDLINE | ID: mdl-32283347

ABSTRACT

The phenomenon of bioluminescence is the most widely investigated model of quorum sensing (QS) that occurs in various strains of Vibrio. Of lately, most of the virulence exhibited by other microbes is also attributed by similar quorum sensing pathways. Any leap towards blocking of such mechanisms is the need of the hour which is hypothesized to be achieved by interfering with normal QS interactions between ligands and their receptors. Gingerol, a pungent oil easily available from ginger is a structural analog of N-acylhomoserine lactone (AHL), which is an actual signalling ligand of QS-receptor LuxR responsible for initiating a cascade of reactions leading to bioluminescence. In-silico study suggested the antagonistic binding of gingerol to LuxR by hydrogen bonding and hydrophobic interactions which should, in theory, reduce bioluminescence. This was corroborated experimentally by rigorous image analysis of luminescence using hue, saturation and luminescence (HSL) values. Hence, we conclude gingerol as a potent QS-inhibitor for LuxR that may also inhibit the other members of AHL-receptor family.


Subject(s)
Catechols/pharmacology , Fatty Alcohols/pharmacology , Luminescent Measurements , Quorum Sensing/drug effects , Repressor Proteins/antagonists & inhibitors , Trans-Activators/antagonists & inhibitors , Vibrio/drug effects , Catechols/chemistry , Dose-Response Relationship, Drug , Fatty Alcohols/chemistry , Ligands , Models, Molecular , Molecular Structure , Repressor Proteins/chemistry , Repressor Proteins/metabolism , Structure-Activity Relationship , Trans-Activators/chemistry , Trans-Activators/metabolism , Vibrio/metabolism
19.
Curr Microbiol ; 77(8): 1800-1810, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32333184

ABSTRACT

Quorum sensing in bacteria is a cell density-dependent phenomenon in which, a community of cells communicate with each other using signalling molecules belonging to various families of which N-acyl homoserine lactone (AHL) is one. AHL acts via ligand-receptor interaction where receptors of AHL differ from species to species, and possess great degree of similarity in conformation at the active site. A macromolecule, LasR, is a receptor protein that binds to N-(3-oxododecanoyl)-L-homoserinelactone (OdDHL), a type of AHL, viz. responsible for biofilm formation in Pseudomonas aeruginosa. Similar macromolecule LuxR, like LasR, found in Vibrio sp. identifies a different AHL, N-(3-oxohexanoyl)-L-homoserine lactone (OhHSL), responsible for the phenomenon of bioluminescence. In silico study depicted that curcumin could bind to both LasR and LuxR by unique sets of hydrogen bonding and hydrophobic interactions that can lead to the inactivation of these proteins, enabling this plant-derived organic AHL antagonist to be categorized as a quorum sensing inhibitor (QSI). To prove this hypothesis, curcumin was treated on P. aeruginosa to access the reduction in biofilm formation and on V. alginolyticus to check its efficacy to reduction in bioluminescence by inhibition of QS. The results of these studies proved curcumin to be an efficient QSI.


Subject(s)
Bacteria/drug effects , Bacterial Proteins/chemistry , Curcumin/pharmacology , Quorum Sensing/drug effects , Repressor Proteins/chemistry , Trans-Activators/chemistry , Acyl-Butyrolactones/chemistry , Bacteria/chemistry , Biofilms , Metabolic Networks and Pathways , Models, Molecular , Molecular Docking Simulation , Protein Binding , Pseudomonas aeruginosa/physiology
20.
J Hazard Mater ; 388: 122047, 2020 04 15.
Article in English | MEDLINE | ID: mdl-31954311

ABSTRACT

Currently, radioactive waste is disposed primarily by burial in a deep geological repository. Microorganisms thriving in such contaminated environment show tolerance to radionuclides. In the present study the bacterial flora, from soil sample collected from an area around atomic power station exposed to radionuclides and heavy metals, was cultivated and assessed for thorium (Th) tolerance. Of all the isolates, strain AM7 identified as O. intermedium was selected since it could thrive at high levels of Th (1000 mg L-1). AM7 was characterized physico-chemically and its culture medium was optimized using central composite design of response surface methodology for assessing its growth properties in presence of Th. The strain also showed exceptional exopolysaccharide (EPS) production and its yield was further analyzed using one factor study to investigate the influence of each medium component. On supplementing the EPS medium with Th, no significant decrease in yield was observed. FTIR spectroscopy revealed the functional groups of EPS involved in EPS-Th binding. To the best of our knowledge, this is the first report showing exceptional Th-tolerance by any bacteria. Such study will help other researchers to strategize an environment-friendly way of radwaste disposal.


Subject(s)
Biopolymers/metabolism , Ochrobactrum/radiation effects , Polysaccharides, Bacterial/metabolism , Radiation Tolerance , Soil Pollutants, Radioactive/pharmacology , Thorium Compounds/pharmacology , Microbial Consortia , Ochrobactrum/genetics , Ochrobactrum/growth & development , Ochrobactrum/metabolism , RNA, Ribosomal, 16S
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