ABSTRACT
For decades, bacterial natural products have served as valuable resources for developing novel drugs to treat several human diseases. Recent advancements in the integrative approach of using genomic and functional tools have proved beneficial in obtaining a comprehensive understanding of these biomolecules. This study presents an in-depth characterization of the anti-diabetic activity exhibited by a bacterial isolate SW1, isolated from an effluent treatment plant. As a primary screening, we assessed the isolate for its potential to inhibit alpha-amylase and alpha-glucosidase enzymes. Upon confirmation, we further utilized LC-MS, ESI-MS/MS, and NMR spectroscopy to identify and characterize the biomolecule. These efforts were coupled with the genomic assessment of the biosynthetic gene cluster involved in the anti-diabetic compound production. Our investigation discovered that the isolate SW1 inhibited both α-amylase and α-glucosidase activity. The chemical analysis suggested the production of acarbose, an anti-diabetic biomolecule, which was further confirmed by the presence of biosynthetic gene cluster "acb" in the genome. Our in-depth chemical characterization and genome mining approach revealed the potential of bacteria from an unconventional niche, an effluent treatment plant. To the best of our knowledge, it is one of the first few reports of acarbose production from the genus Arthrobacter.
Subject(s)
Arthrobacter , Acarbose , Arthrobacter/genetics , Genomics , Glycoside Hydrolase Inhibitors , Humans , Tandem Mass Spectrometry , alpha-Glucosidases/geneticsABSTRACT
INTRODUCTION: Fibrous Dysplasia is a relatively rare Musculoskeletal disorders in which there is a defect in remodelling of immature bone to mature lamellar bone. Fibrous Dysplasia was first described by Von Recklinghausen in 1891, but it was Lichtenstein who labelled it polyostotic Fibrous Dysplasia in 1938. Union of Pathological Fractures in a bone affected by Fibrous Dysplasia poses a difficult set of Challenges for treating Physicians. CASE REPORT: We Report a 24 year-old female patient with a Pathological Fracture of the Tibia in a Monostotic Anterior Cortical Fibrous Dysplasia Hybrid Fixation with a UnicorticalOsteoperisoteal Non Vascularized Fibula Graft with a follow up until the union of fracture site on computed tomography scan and complete integration of unicorticalosteoperiosteal fibular graft . CONCLUSION: We provide additional and independent evidence that removal of the diseased cortex which were parts of the proximal and distal fragment and reconstruction of the defect in the cortex with a press- fitunicortical Non vascularized osteoperiosteal fibular strut graft with a hybrid fixation is a good treatment modality for monostotic fibrous dysplasia. Hybrid fixation includes retrograde intramedullary transarticular rodding extending across the subtalar and ankle joint into the tibia and augmentation of the primary fixation with a mono-planar rail Fixation in compression mode.
ABSTRACT
BACKGROUND: Despite high vaccination coverage using acellular (ACV) and whole-cell pertussis (WCV) vaccines, the resurgence of pertussis is observed globally. Genetic divergence in circulating strains of Bordetella pertussis has been reported as one of the contributing factors for the resurgence of the disease. Our current knowledge of B. pertussis genetic evolution in circulating strains is mostly based on studies conducted in countries using ACVs targeting only a few antigens used in the production of ACVs. To better understand the adaptation to vaccine-induced selection pressure, it will be essential to study B. pertussis populations in developing countries which are using WCVs. India is a significant user and global supplier of WCVs. We report here comparative genome analyses of vaccine and clinical isolates reported from India. Whole-genome sequences obtained from vaccine strains: WCV (J445, J446, J447 and J448), ACV (BP165) were compared with Tohama-I reference strain and recently reported clinical isolates from India (BPD1, BPD2). Core genome-based phylogenetic analysis was also performed using 166 isolates reported from countries using ACV. RESULTS: Whole-genome analysis of vaccine and clinical isolates reported from India revealed high genetic similarity and conserved genome among strains. Phylogenetic analysis showed that clinical and vaccine strains share genetic closeness with reference strain Tohama-I. The allelic profile of vaccine strains (J445:ptxP1/ptxA2/prn1/fim2-1/fim3-1; J446: ptxP2/ptxA4/prn7/fim2-2/fim3-1; J447 and J448: ptxP1/ptxA1/ prn1/fim2-1/fim3-1), which matched entirely with clinical isolates (BPD1:ptxP1/ptxA1/prn1/fim2-1 and BPD2: ptxP1/ptxA1/prn1/fim2-1) reported from India. Multi-locus sequence typing (MLST) demonstrated the presence of dominant sequence types ST2 and primitive ST1 in vaccine strains which will allow better coverage against circulating strains of B. pertussis. CONCLUSIONS: The study provides a detailed characterization of vaccine and clinical strains reported from India, which will further facilitate epidemiological studies on genetic shifts in countries which are using WCVs in their immunization programs.
Subject(s)
Bordetella pertussis/genetics , Genome, Bacterial/genetics , Pertussis Vaccine/genetics , Bordetella pertussis/classification , Bordetella pertussis/immunology , Bordetella pertussis/isolation & purification , Genes, Bacterial/genetics , Genetic Variation , Genomics , Genotype , Humans , Pertussis Vaccine/classification , Phylogeny , Whooping Cough/microbiology , Whooping Cough/prevention & controlABSTRACT
The stress response forms the most ancient defense system in living cells. Heat shock proteins (Hsps) are highly conserved across species and play major roles in mounting the stress response. The emerging information now suggests that Hsp90 family of chaperones display additional cellular roles contributing to diseases like cancer. For this reason, pharmacological targeting of Hsp90 has emerged as a novel antitumor strategy. However, its mitochondrial homologue TRAP1 has not been implicated in cancer with conclusive mechanistic insights. Since understanding the mutational spectrum of cancer cells indicates the outcome of the disease as well as treatment response, we examined mutational spectrum of TRAP1. Our in silico analyses of TRAP1 SNPs and CNVs correlated with the aggressive cancer phenotypes, and are found to be predominant over Hsp90 itself. The increased CNVs have been correlated with increased expression of TRAP1 in metastatic cancer cells, increased ATP production, and decreased oxygen consumption rate of mitochondria. Examining TRAP1 knockdown as well as over expression in metastatic cancer cells furthered our understanding that TRAP1 likely to facilitate the altered energy metabolism in the functional compromise of mitochondrial OXPHOS. Interestingly, the increased ATP levels in the TRAP1 background are found to be independent of glucose oxidation. Our results suggest TRAP1 role in triggering the alternate energy metabolism in cancer cells. Since targeting tumor metabolism is considered as an alternate strategy to combat cancer, we propose pharmacological targeting of TRAP1 to target alternate energy metabolism.
Subject(s)
HSP90 Heat-Shock Proteins/metabolism , Mitochondria/metabolism , Neoplasms/metabolism , Polymorphism, Single Nucleotide , Cell Line , DNA Copy Number Variations , Gene Expression Regulation, Neoplastic , HSP90 Heat-Shock Proteins/genetics , Humans , Neoplasms/genetics , Oxygen Consumption , Protein Isoforms/chemistry , Protein Isoforms/genetics , Protein Isoforms/metabolismABSTRACT
H-Bonding abilities of ionic liquids (ILs) along with hydrophobicity and cooperativity effects increases their hydration numbers making them capable for dissolving sparingly soluble organic molecules in aqueous or polar nonaqueous media, and hence ILs are potential candidates in pharmaceutical and medicinal sciences besides the different technological and academic interests. In this work, dielectric spectra were measured and analyzed for diethylammonium-based protic ionic liquids (PILs), imidazolium-based aprotic ionic liquids (APILs), and their aqueous solutions (â¼0.02 to â¼0.8 mol·dm-3) over a frequency range from 0.01 to 50 GHz using time domain reflectometry at 298.15 K. The Cole-Cole (CC) model for neat ILs and a combination of the Debye and Cole-Cole (D+CC) models for their aqueous solutions best describes the experimental dielectric relaxation spectra. Higher values of static permittivity and relaxation time were observed for less viscous PILs compared to more viscous APILs due to the existence of hydrogen bonding in PILs, ionic translational motion, and the existence of transient, short-lived proton transfer responsible for solvent polarization. For aqueous solutions of ionic liquids, the fast collective relaxation of solvent (bulk water) observed at higher frequencies (â¼20 GHz) and slow relaxation is detected at lower frequency (â¼5 to â¼10 GHz) due to hydrophobic hydration with or without cooperative H-bonding effect. The apparent concentrations of bulk water, cbwap, and slow water, cswap, were used to obtain effective hydration numbers to understand the ion solvation. Hydration numbers revealed that imidazolium-based APILs are weakly hydrated than the diethylammonium-based PILs. Static permittivity and relaxation time of pure ILs and of aqueous solutions of studied ILs are discussed in terms of effect on alkyl chain length of cation/anion, H-bonding abilities of ions, dipole moments of ions, viscosity, hydrophobic effects, etc.
ABSTRACT
Whole-cell and acellular pertussis vaccines are used globally against Bordetella pertussis Various vaccine reference strains are used globally for the production of such vaccines. We report here a draft genome sequence for Bordetella pertussis strain BP 165, which is used by the Serum Institute of India in the production of acellular pertussis vaccine.
ABSTRACT
A dark-coloured effluent called "spent wash" is generated as an unwanted product in sugarcane-based alcohol distilleries. Most distilleries discharge this effluent into soil or water without any treatment, causing water and soil pollution. Herein, we report chromium-doped TiO2 (Cr-TiO2) as a photocatalyst for the degradation of spent wash colour under natural sunlight. Cr-doped TiO2 nanoparticles were prepared using an aqueous titanium peroxide-based sol-gel method with titanium isopropoxide as the Ti precursor and chromium nitrate as the Cr precursor. To observe the effect of dopant on sol-gel behaviour and physicochemical properties, the Cr concentration was varied in the range 0.5-5 wt%. The crystallization temperature and time were optimized to obtain the required phase of Cr-TiO2. The physicochemical characteristics of the Cr-doped TiO2 catalyst were determined using X-ray diffraction, FE-SEM, FETEM, TG, XPS, the Brunauer-Emmett-Teller (BET) method, FT-IR, Raman, PL, ICP-MS, and UV visible spectroscopy. A shift in the absorption edge of TiO2 by doping with chromium suggested an increase in visible light absorption due to a decrease in the effective band gap. The application potential of the Cr-TiO2 catalyst was studied in the degradation of sugar-based alcohol distillery waste under natural sunlight, and the results were compared with those of undoped TiO2 and Degussa P25 TiO2. Degradation of the spent wash solution was monitored using UV-visible, gel permeation chromatography (GPC), and QTOF LC-MS. GPC and LC-MS showed significant changes in the molecular weight of spent wash colour-forming compounds due to the degradation reaction. QTOF LC-MS analysis suggested that acids, alcohols, glucosides, ketones, lipids, peptides, and metabolites were oxidized to low-molecular-weight counterparts. From the results, 5% Cr-TiO2 showed the highest degradation rate among all Cr-TiO2 samples, undoped TiO2, and Degussa P25 TiO2 under identical reaction conditions, with nearly 68-70% degradation achieved in 5 h.
ABSTRACT
One-pot green synthesis of propargylamines using ZnCl2 loaded TiO2 nanomaterial under solvent-free conditions has been effectively accomplished. The aromatic aldehydes, amines, and phenylacetylene were reacted at 100 °C in the presence of the resultant catalyst to form propargylamines. The nanocrystalline TiO2 was initially synthesized by a sol-gel method from titanium(iv) isopropoxide (TTIP) and further subjected to ZnCl2 loading by a wet impregnation method. X-ray diffraction (XRD) patterns revealed the formation of crystalline anatase phase TiO2. Field emission scanning electron microscopy (FESEM) showed the formation of agglomerated spheroid shaped particles having a size in the range of 25-45 nm. Transmission electron microscopy (TEM) validates cubical faceted and nanospheroid-like morphological features with clear faceted edges for the pure TiO2 sample. Surface loading of ZnCl2 on spheroid TiO2 nanoparticles is evident in the case of the ZnCl2 loaded TiO2 sample. X-ray photoelectron spectroscopy (XPS) confirmed the presence of Ti4+ and Zn2+ species in the ZnCl2 loaded TiO2 catalyst. Energy-dispersive X-ray (EDS) spectroscopy also confirmed the existence of Ti, O, Zn and Cl elements in the nanostructured catalyst. 15% ZnCl2 loaded TiO2 afforded the highest 97% yield for 3-(1-morpholino-3-phenylprop-2-ynyl)phenol, 2-(1-morpholino-3-phenylprop-2-ynyl)phenol and 4-(1,3-diphenylprop-2-ynyl)morpholine under solvent-free and aerobic conditions. The proposed nanostructure-based heterogeneous catalytic reaction protocol is sustainable, environment-friendly and offers economic viability in terms of recyclability of the catalyst.
ABSTRACT
BACKGROUND: Enterococcus faecium though commensal in the human gut, few strains provide a beneficial effect to humans as probiotics while few are responsible for the nosocomial infection. Comparative genomics of E. faecium can decipher the genomic differences responsible for probiotic, pathogenic and non-pathogenic properties. In this study, we compared E. faecium strain 17OM39 with a marketed probiotic, non-pathogenic non-probiotic (NPNP) and pathogenic strains. RESULTS: E. faecium 17OM39 was found to be closely related with marketed probiotic strain T110 based on core genome analysis. Strain 17OM39 was devoid of known vancomycin, tetracycline resistance and functional virulence genes. Moreover, E. faecium 17OM39 genome was found to be more stable due to the absence of frequently found transposable elements. Genes imparting beneficial functional properties were observed to be present in marketed probiotic T110 and 17OM39 strains. Genes associated with colonization and survival within gastrointestinal tract was also detected across all the strains. CONCLUSIONS: Beyond shared genetic features; this study particularly identified genes that are responsible for imparting probiotic, non-pathogenic and pathogenic features to the strains of E. faecium. Higher genomic stability, absence of known virulence factors and antibiotic resistance genes and close genomic relatedness with marketed probiotics makes E. faecium 17OM39 a potential probiotic candidate. The work presented here demonstrates that comparative genome analyses can be applied to large numbers of genomes, to find potential probiotic candidates.
Subject(s)
Bacterial Proteins/genetics , Drug Resistance, Microbial , Enterococcus faecium/genetics , Genome, Bacterial , Gram-Positive Bacterial Infections/microbiology , Probiotics , Virulence/drug effects , Anti-Bacterial Agents/pharmacology , Enterococcus faecium/drug effects , Enterococcus faecium/isolation & purification , Gastrointestinal Tract/microbiology , Genomics , Humans , Virulence FactorsABSTRACT
A cross-sectional survey was conducted across 320 chemists shop in Pune city for their availability and labeling practices. The questionnaire revealed the data about the most sold probiotic preparations, their mode of sale, and their available forms such as tablet, capsule, and sachet. Top ten probiotic preparations were evaluated for labeling practice as per the existing regulations of the Indian Council of Medical Research-Department of Biotechnology, Indian guidelines. Majority of probiotic preparations were listing the best before date, viability, probiotic organisms, net quantity, and batch number, but none of them mentioned the health claims.
Subject(s)
Pharmacists/statistics & numerical data , Probiotics/supply & distribution , Cross-Sectional Studies , Humans , India , Marketing , Surveys and QuestionnairesABSTRACT
The human gut microbiome plays a crucial role in human health and efforts need to be done for cultivation and characterisation of bacteria with potential health benefits. Here, we isolated a bacterium from a healthy Indian adult faeces and investigated its potential as probiotic. The cultured bacterial strain 17OM39 was identified as Enterococcus faecium by 16S rRNA gene sequencing. The strain 17OM39 exhibited tolerance to acidic pH, showed antimicrobial activity and displayed strong cell surface traits such as hydrophobicity and autoaggregation capacity. The strain was able to tolerate bile salts and showed bile salt hydrolytic (BSH) activity, exopolysaccharide production and adherence to human HT-29 cell line. Importantly, partial haemolytic activity was detected and the strain was susceptible to the human serum. Genomics investigation of strain 17OM39 revealed the presence of diverse genes encoding for proteolytic enzymes, stress response systems and the ability to produce essential amino acids, vitamins and antimicrobial compound Bacteriocin-A. No virulence factors and plasmids were found in this genome of the strain 17OM39. Collectively, these physiological and genomic features of 17OM39 confirm the potential of this strain as a candidate probiotic.
Subject(s)
Enterococcus faecium/genetics , Genome, Bacterial , Adult , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Enterococcus faecium/isolation & purification , Enterococcus faecium/metabolism , Feces/microbiology , HT29 Cells , Hemolysis , Humans , Peptide Hydrolases/genetics , Peptide Hydrolases/metabolism , Polysaccharides, Bacterial/metabolism , Probiotics/isolation & purification , Probiotics/metabolism , RNA, Ribosomal, 16S/genetics , Salt ToleranceABSTRACT
Waste from the sugar cane industry and alcohol distilleries is one of the sources of water pollution, and the degradation of this effluent is a very challenging task. Photocatalytic degradation can be an attractive alternative to conventional degradation processes. A vanadium-doped TiO2 (V-TiO2) photocatalyst for the degradation of spent wash and industrial dyes has been studied and reported here. V-doped TiO2 nanoparticles were prepared using a sol-gel method based on aqueous titanium peroxide with titanium isopropoxide as the Ti precursor and V2O5 as the V precursor. In order to observe the effect of the dopant on sol-gel behaviour, physicochemical and structural properties, the concentration of V was varied between 1.0% and 5% by weight. The crystallization temperature and time were optimized to obtain the required phase of V-TiO2. The physicochemical and structural characteristics of the V-doped TiO2 catalyst were determined using Brunauer-Emmett-Teller (BET), X-ray diffraction, FESEM, TEM, TG, FT-IR, Raman, PL and UV-visible spectroscopic techniques. UV-visible analysis showed a red shift in the absorption edge of TiO2 upon doping with V metal, which suggested an increase in the absorption of visible light due to a decrease in the effective band gap. The application potential of the V-TiO2 catalyst was studied via the degradation of sugar industry waste (spent wash) and Jakofix red dye (HE 8BN) under natural sunlight, as well as a standard artificial solar energy source (Xe lamp). The highest activity was observed for a 1% V-TiO2 photocatalyst for the degradation of spent wash and Jakofix red dye under natural sunlight. The degradation of coloured compounds in spent wash was monitored by gel permeation chromatography (GPC), which showed the degradation of high-molecular-weight compounds into low-molecular-weight fractions. The catalyst decomposed 90% of Jakofix red dye (HE 8BN) in 3.5 h and 65% of spent wash in 5 h under irradiation with natural sunlight, whereas Degussa P-25 TiO2 was only able to decompose 35% of the dye and 20% of spent wash under identical reaction conditions. A cycling stability test showed the high stability and reusability of the photocatalyst for degradation reactions, with a recovery of around 94-96%.
ABSTRACT
Genomic studies provide deeper insights into secondary metabolites produced by diverse bacterial communities, residing in various environmental niches. This study aims to understand the potential of a biosurfactant producing Bacillus sp. AM13, isolated from soil. An integrated approach of genomic and chemical analysis was employed to characterize the antibacterial lipopeptide produced by the strain AM13. Genome analysis revealed that strain AM13 harbors a nonribosomal peptide synthetase (NRPS) cluster; highly similar with known biosynthetic gene clusters from surfactin family: lichenysin (85 %) and surfactin (78 %). These findings were substantiated with supplementary experiments of oil displacement assay and surface tension measurements, confirming the biosurfactant production. Further investigation using LCMS approach exhibited similarity of the biomolecule with biosurfactants of the surfactin family. Our consolidated effort of functional genomics provided chemical as well as genetic leads for understanding the biochemical characteristics of the bioactive compound.
Subject(s)
Bacillus/genetics , Bacterial Proteins/metabolism , Peptide Synthases/genetics , Surface-Active Agents/metabolism , Bacillus/metabolism , Bacterial Proteins/biosynthesis , Bacterial Proteins/genetics , Genome, Bacterial , Genomics , Peptide Synthases/isolation & purification , Secondary Metabolism/geneticsABSTRACT
INTRODUCTION: Vasarishta built upon Mritasanjeevani Sura (MS) is a polyherbal hydro-alcoholic anti-asthmatic formulation which is administered in a dose of 1 ml instead of standard dose 40 ml, generally advocated for any "Asava-Arishta" in Ayurveda. AIM: The present study was aimed at finding out rationale for the peculiar distillation process to manufacture MS followed by Sthapana process to make Vasarishta. It was further aimed to find out difference in Vasarishta samples manufactured by purely fermentation process and the peculiar method mentioned above. MATERIALS AND METHODS: Three batches of MS and subsequently three batches of Vasarishta were prepared. Basic standardization and development of standard operating procedure for the same were achieved by doing pH, percentage of alcohol and total reducing sugar, specific gravity on both MS and Vasarishta, during and after completion of process. Finally, MS and Vasarishta (built upon MS) made in laboratory were compared with marketed samples of MS and Vasarishta using gas chromatography. RESULTS: The types of alcohols and volatile acids in MS and Vasarishta, prepared in laboratory, are similar but the proportions differ, which is taken as an indicator of process standardization. Values of furfural, ethyl acetate, and 1-butanol in lab samples are within permissible limits as against the values of the market samples. CONCLUSIONS: The textual process for the production of Vasarishta proved to produce organoleptically acceptable product which is virtually free of toxic compounds such as furfural.
ABSTRACT
A novel Gram-negative, motile, rod-shaped, facultative anaerobic bacterial strain, KMK6(T), was isolated from soil contaminated with textile dyes from an industrial estate located at Ichalkaranji, Maharashtra, India, and its taxonomical position was established by using a polyphasic approach. The major cellular fatty acids included C17:1ω8c, summed feature 3 (C16:1ω7c and/or iso-C15:0 2-OH), C17:0, C16:0, and C18:1ω7c. The DNA G+C content of strain KMK6(T) was 48.8 mol %. 16S rRNA gene sequence analysis confirmed its placement in the genus Alishewanella, and exhibited sequence similarity levels of below 97 % to the type strains of validly published Alishewanella species. On the basis of genotypic and phenotypic evidence, strains KMK6(T) is considered to be a novel species of the genus Alishewanella, for which we propose that strain KMK6(T) (=NCIM 5295(T) =BCRC 17848(T)) is assigned to a novel species, Alishewanella solinquinati sp. nov.
Subject(s)
Alteromonadaceae/isolation & purification , Alteromonadaceae/metabolism , Coloring Agents/metabolism , Soil Microbiology , Soil Pollutants/metabolism , Alteromonadaceae/classification , Alteromonadaceae/genetics , Biodegradation, Environmental , Coloring Agents/analysis , Molecular Sequence Data , Phylogeny , Soil/chemistry , Soil Pollutants/analysis , TextilesABSTRACT
A lipolytic mesophilic fungus which produces lipase extracellularly was isolated from soil. Based on ITS1-5.8S-ITS4 region sequences of ribosomal RNA, it was concluded that the isolate JK-1 belongs to genus Rhizopus and clades with Rhizopus oryzae. The present paper reports the screening, isolation, identification, and optimization of fermentation conditions for the production of lipase (EC 3.1.1.3). Culture conditions were optimized, and the highest lipase production was observed in basal medium with corn steep liquor as nitrogen source and glucose as carbon source. Maximum lipase production was observed at 72 h, which is about 870 U/ml. Optimization of fermentation conditions resulted in 16-fold enhancement in enzyme production.
Subject(s)
Bacterial Proteins , Biotechnology/methods , Lipase , Rhizopus/enzymology , Soil Microbiology , Bacterial Proteins/biosynthesis , Bacterial Proteins/metabolism , Carbon/metabolism , Culture Media , DNA, Bacterial/analysis , Fermentation , Glucose/metabolism , Hydrogen-Ion Concentration , Kinetics , Lipase/biosynthesis , Lipase/metabolism , Nitrogen/metabolism , Phylogeny , Rhizopus/classification , Rhizopus/genetics , Rhizopus/isolation & purification , Sequence Analysis, DNA , Temperature , Zea mays/metabolismABSTRACT
BACKGROUND: Temsirolimus is a mammalian target of rapamycin (mTOR) inhibitor and rapamycin analogue that is approved for treating advanced renal cell carcinoma (RCC). It is being actively evaluated in clinical trials for melanoma. The mTOR inhibitors are also immunosuppressants and are used clinically to prevent rejection following solid-organ transplant. Novel immunotherapies are being actively developed for immunoresponsive tumours, such as RCC and melanoma. METHODS: Immune-modulating effects of temsirolimus were characterised when used in combination with cancer vaccines targeting RCC (RENCA) and melanoma (B16). Cancer vaccines were recombinant tumour-specific proteins (CA9 or gp100), and recombinant heat shock protein (HSP; hsp110) served as the immune adjuvant. RESULTS: In murine models, temsirolimus enhanced the anti-tumour activity of cancer vaccines used to treat established RENCA and B16 tumours. A tumour prevention model established that the enhanced anti-tumour activity associated with temsirolimus was immune mediated. In mice treated with an HSP-based anti-tumour vaccine, temsirolimus-treated CD8 T cells had greater interferon-γ and cytotoxic T-cell responses when compared with mice treated with vaccine alone. Temsirolimus also enhanced the formation of CD8 memory cells following administration of HSP-based cancer vaccine. CONCLUSION: These results provide a rationale for combining mTOR inhibitor with immunotherapy when treating immunoresponsive tumours.
Subject(s)
Cancer Vaccines/therapeutic use , Carcinoma, Renal Cell/therapy , Heat-Shock Proteins/antagonists & inhibitors , Kidney Neoplasms/therapy , Melanoma, Experimental/therapy , Sirolimus/analogs & derivatives , TOR Serine-Threonine Kinases/antagonists & inhibitors , Animals , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/pharmacology , Cancer Vaccines/administration & dosage , Carcinoma, Renal Cell/immunology , Carcinoma, Renal Cell/pathology , Cells, Cultured , Drug Synergism , Heat-Shock Proteins/immunology , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/therapeutic use , Immunotherapy/methods , Kidney Neoplasms/immunology , Kidney Neoplasms/pathology , Melanoma, Experimental/immunology , Melanoma, Experimental/pathology , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Protein Kinase Inhibitors/administration & dosage , Protein Kinase Inhibitors/pharmacology , Sirolimus/administration & dosage , Sirolimus/pharmacologyABSTRACT
Siderophoregenic Bacillus strain DET9 has been selectively isolated from dairy waste. It was evaluated for probiotic characteristics and susceptibility pattern against antibiotics. Its spores showed excellent tolerance to simulated gastrointestinal tract conditions and exhibited antimicrobial activity against organisms such as Escherichia coli, Micrococcus flavus, and Staphylococcus aureus. Its susceptibility to antibiotics reduces the prospect to donate resistance determinants if administered in the form of probiotic preparations. It was observed to produce approximately 60 mg/l catecholate type of siderophore under iron stressed conditions, identified as a 2,3-dihydroxy benzoic acid by high-performance liquid chromatography, infrared spectroscopy, nuclear magnetic resonance, and mass spectral analysis. Partial 16S-rRNA gene sequencing analysis shows that the isolate exhibited homology with Bacillus thuringiensis and Bacillus weihenstephanensis, whereas biochemical characterization revealed its novelty. DET9 exhibited no mortality of fishes in a 60-day trial, when fishes (surfi tetra) were challenged up to 100 ppm cell concentration, with their daily diet.
Subject(s)
Bacillus/isolation & purification , Bacillus/physiology , Dairy Products/microbiology , Industrial Waste , Probiotics/metabolism , Siderophores/biosynthesis , Animals , Anti-Bacterial Agents/pharmacology , Bacillus/drug effects , Bacillus/genetics , Bacterial Adhesion , Base Sequence , Bile Acids and Salts/pharmacology , Catalase/metabolism , Diet , Fishes/microbiology , Fishes/physiology , Gastric Acid , Hemolysis , Humans , Hydrophobic and Hydrophilic Interactions , Iron/metabolism , Molecular Sequence Data , Phylogeny , Probiotics/administration & dosage , Spores, Bacterial/genetics , Spores, Bacterial/metabolism , Spores, Bacterial/physiologyABSTRACT
The release of azo dyes into the environment is a concern due to coloration of natural waters and due to the toxicity, mutagenicity and carcinogenicity of the dyes and their biotransformation products. The dye degrading bacterial strain KMK 5 was isolated from the textile dyes contaminated soil of Ichalkaranji, Maharashtra, India. It was identified as Bacillus fusiformis based on the biochemical and morphological characterization as well as 16S rDNA sequencing. KMK 5 could tolerate and degrade azo dyes, Disperse Blue 79 (DB79) and Acid Orange 10 (AO10) under anoxic conditions. Complete mineralization of DB79 and AO10 at the concentration of 1.5g/l was observed within 48h. This degradation potential increased the applicability of this microorganism for the dye removal.