scholarly journals Role of Molecular Interactions and Oligomerization in Chaperone Activity of Recombinant Acr from Mycobacterium tuberculosis

2019 ◽  
Vol 17 (3) ◽  
pp. 55-62
Author(s):  
Gautam Krishnan ◽  
Utpal Roy
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Molecular Interactions ◽  
Chaperone Activity

scholarly journals Prediction of recombinant Mycobacterium tuberculosis α-crystallin oligomer chaperone activity using polynomial graphs

F1000Research ◽  
2020 ◽  
Vol 7 ◽  
pp. 1801
Author(s):  
Gautam Krishnan ◽  
Utpal Roy
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Molecular Level ◽  
Gel Filtration ◽  
Chaperone Activity ◽  
Oligomeric State ◽  
Dynamic Nature ◽  
Order Coefficient ◽  
The One

Background: Mycobacterial α-crystallin (Acr) is a chaperone that prevents misfolding of proteins when Mycobacterium tuberculosis is found in a latent form in the host tissue. Methods: Using insulin as a model substrate and utilizing polynomial graphs, we attempted to predict molecular-level interactions that are a function of the oligomeric state of the recombinant protein. The chaperone activity of the recombinant oligomeric Acr was measured at 60°C with Acr samples obtained before gel filtration chromatography and compared with a gel-filtered sample. Results: The polynomial graphs constructed showed improved molecular coverage of the insulin B chain by the oligomer. The 2nd order coefficient is the one that changes with the oligomeric ratio of Acr and improves chaperone activity. Polynomial analysis suggested that it could be a useful parameter to predict chaperone activity for potential in vitro batches of M. tuberculosis Acr based on the dynamic nature of the association and disassociation of oligomers. Conclusions: The results showed that coverage of insulin B chain improved with higher ratio of 9-mer as compared to lower ratios. This was shown by both simulation plots and actual assay data. The polynomial graphs showed increase in the 2nd order coefficient, thus suggesting the important role of oligomerisation in improved molecular coverage of insulin B chain.

scholarly journals Prediction of recombinant Mycobacterium tuberculosis α-crystallin oligomer chaperone activity using polynomial graphs

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1801
Author(s):  
Gautam Krishnan ◽  
Utpal Roy
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Molecular Level ◽  
Gel Filtration ◽  
Chaperone Activity ◽  
Oligomeric State ◽  
Dynamic Nature ◽  
Order Coefficient ◽  
The One

Background: Mycobacterial α-crystallin (Acr) is a chaperone that prevents misfolding of proteins when Mycobacterium tuberculosis is found in a latent form in the host tissue. Methods: Using insulin as a model substrate and utilizing polynomial graphs, we attempted to predict molecular-level interactions that are a function of the oligomeric state of the recombinant protein. The chaperone activity of the recombinant oligomeric Acr was measured at 60°C with Acr samples obtained before gel filtration chromatography and compared with a gel-filtered sample. Results: The polynomial graphs constructed showed improved molecular coverage of the insulin B chain by the oligomer. The 2nd order coefficient is the one that changes with the oligomeric ratio of Acr and improves chaperone activity. Polynomial analysis suggested that it could be a useful parameter to predict chaperone activity for potential in vitro batches of M. tuberculosis Acr based on the dynamic nature of the association and disassociation of oligomers. Conclusions: The results showed that coverage of insulin B chain improved with higher ratio of 9-mer as compared to lower ratios. This was shown by both simulation plots and actual assay data. The polynomial graphs showed increase in the 2nd order coefficient, thus suggesting the important role of oligomerisation in improved molecular coverage of insulin B chain.

scholarly journals Role of the Anilinium Ion on the Selective Polymerization of Anilinium 2-Acrylamide-2-methyl-1-propanesulfonate

Polymers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 2349
Author(s):  
Alain Salvador Conejo-Dávila ◽  
Marco Armando Moya-Quevedo ◽  
David Chávez-Flores ◽  
Alejandro Vega-Rios ◽  
Erasto Armando Zaragoza-Contreras
Keyword(s):  
Cyclic Voltammetry ◽  
Optical Properties ◽  
Thermal Properties ◽  
Free Radical ◽  
1H Nmr ◽  
Molecular Interactions ◽  
13C Nmr ◽  
Oxidative Polymerization ◽  
Cyclic Voltammetry Analysis

The development of anilinium 2-acrylamide-2-methyl-1-propanesulfonate (Ani-AMPS) monomer, confirmed by 1H NMR, 13C NMR, and FTIR, is systematically studied. Ani-AMPS contains two polymerizable functional groups, so it was submitted to selective polymerization either by free-radical or oxidative polymerization. Therefore, poly(anilinium 2-acrylamide-2-methyl-1-propanesulfonic) [Poly(Ani-AMPS)] and polyaniline doped with 2-acrylamide-2-methyl-1-propanesulfonic acid [PAni-AMPS] can be obtained. First, the acrylamide polymer, poly(Ani-AMPS), favored the π-stacking of the anilinium group produced by the inter- and intra-molecular interactions and was studied utilizing 1H NMR, 13C NMR, FTIR, and UV-Vis-NIR. Furthermore, poly(Ani-AMPS) fluorescence shows quenching in the presence of Fe2+ and Fe3+ in the emission spectrum at 347 nm. In contrast, the typical behavior of polyaniline is observed in the cyclic voltammetry analysis for PAni-AMPS. The optical properties also show a significant change at pH 4.4. The PAni-AMPS structure was corroborated through FTIR, while the thermal properties and morphology were analyzed utilizing TGA, DSC (except PAni-AMPS), and FESEM.

scholarly journals Obesity-Induced Dysbiosis Exacerbates IFN-γ Production and Pulmonary Inflammation in the Mycobacterium tuberculosis Infection

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1732
Author(s):  
Sandra Patricia Palma Albornoz ◽  
Thais Fernanda de Campos Fraga-Silva ◽  
Ana Flávia Gembre ◽  
Rômulo Silva de Oliveira ◽  
Fernanda Mesquita de Souza ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Gut Microbiota ◽  
Inflammatory Diseases ◽  
Pulmonary Inflammation ◽  
Host Susceptibility ◽  
Chronic Infections ◽  
Mycobacterium Tuberculosis Infection ◽  
Pulmonary Damage ◽  
Ifn Γ

The microbiota of the gut–lung axis affects local and far-reaching immune responses and might also trigger chronic and inflammatory diseases. We hypothesized that gut dysbiosis induced by obesity, which coexists in countries with a high tuberculosis burden, aggravates the host susceptibility and the pulmonary damage tolerance. To assess our hypothesis, we used a model of high-fat diet (HFD)-induced obesity, followed by infection of C57BL/6 mice with Mycobacterium tuberculosis. We showed that obesity increased the susceptibility, the pulmonary inflammation and IFN-γ levels in M. tuberculosis-infected mice. During the comorbidity obesity and tuberculosis, there is an increase of Bacteroidetes and Firmicutes in the lungs, and an increase of Firmicutes and butyrate in the feces. Depletion of gut microbiota by antibiotic treatment in the obese infected mice reduced the frequencies of CD4+IFN-γ+IL-17− cells and IFN-γ levels in the lungs, associated with an increase of Lactobacillus. Our findings reinforce the role of the gut–lung axis in chronic infections and suggest that the gut microbiota modulation may be a potential host-directed therapy as an adjuvant to treat TB in the context of IFN-γ-mediated immunopathology.

scholarly journals Mutation ofRv2887, amarR-Like Gene, Confers Mycobacterium tuberculosis Resistance to an Imidazopyridine-Based Agent

2015 ◽  
Vol 59 (11) ◽  
pp. 6873-6881 ◽  
Author(s):  
Kathryn Winglee ◽  
Shichun Lun ◽  
Marco Pieroni ◽  
Alan Kozikowski ◽  
William Bishai
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Drug Targets ◽  
Efflux Pump ◽  
Transcriptional Regulator ◽  
Cross Resistance ◽  
Loss Of Function ◽  
Strong Activity ◽  
Content Type ◽  
Novel Drug

ABSTRACTDrug resistance is a major problem inMycobacterium tuberculosiscontrol, and it is critical to identify novel drug targets and new antimycobacterial compounds. We have previously identified an imidazo[1,2-a]pyridine-4-carbonitrile-based agent, MP-III-71, with strong activity againstM. tuberculosis. In this study, we evaluated mechanisms of resistance to MP-III-71. We derived three independentM. tuberculosismutants resistant to MP-III-71 and conducted whole-genome sequencing of these mutants. Loss-of-function mutations inRv2887were common to all three MP-III-71-resistant mutants, and we confirmed the role ofRv2887as a gene required for MP-III-71 susceptibility using complementation. The Rv2887 protein was previously unannotated, but domain and homology analyses suggested it to be a transcriptional regulator in the MarR (multiple antibiotic resistance repressor) family, a group of proteins first identified inEscherichia colito negatively regulate efflux pumps and other mechanisms of multidrug resistance. We found that two efflux pump inhibitors, verapamil and chlorpromazine, potentiate the action of MP-III-71 and that mutation ofRv2887abrogates their activity. We also used transcriptome sequencing (RNA-seq) to identify genes which are differentially expressed in the presence and absence of a functional Rv2887 protein. We found that genes involved in benzoquinone and menaquinone biosynthesis were repressed by functional Rv2887. Thus, inactivating mutations ofRv2887, encoding a putative MarR-like transcriptional regulator, confer resistance to MP-III-71, an effective antimycobacterial compound that shows no cross-resistance to existing antituberculosis drugs. The mechanism of resistance ofM. tuberculosisRv2887mutants may involve efflux pump upregulation and also drug methylation.

scholarly journals Inflammasomes inMycobacterium tuberculosis-Driven Immunity

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Sebastian Wawrocki ◽  
Magdalena Druszczynska
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Inflammatory Response ◽  
Immune Responses ◽  
Proinflammatory Cytokines ◽  
Immune Cells ◽  
Protein Complexes ◽  
Inflammasome Activation ◽  
Host Immune Responses ◽  
Multimeric Protein

The development of effective innate and subsequent adaptive host immune responses is highly dependent on the production of proinflammatory cytokines that increase the activity of immune cells. The key role in this process is played by inflammasomes, multimeric protein complexes serving as a platform for caspase-1, an enzyme responsible for proteolytic cleavage of IL-1βand IL-18 precursors. Inflammasome activation, which triggers the multifaceted activity of these two proinflammatory cytokines, is a prerequisite for developing an efficient inflammatory response against pathogenicMycobacterium tuberculosis(M.tb). This review focuses on the role of NLRP3 and AIM2 inflammasomes inM.tb-driven immunity.

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