Iron homeostasis is highly regulated in organisms across evolutionary time scale as iron is essential for various cellular processes. In a computational screen, we identified the Yap/bZIP domain family in Candida clade genomes. Cap2/Hap43 is essential for C. albicans growth under iron-deprivation conditions and for virulence in mouse. Cap2 has an amino-terminal bipartite domain comprising a fungal-specific Hap4-like domain and a bZIP domain. Our mutational analyses showed that both the bZIP and Hap4-like domains perform critical and independent functions for growth under iron-deprivation conditions. Transcriptome analysis conducted under iron-deprivation conditions identified about 16% of the C. albicans ORFs that were differentially regulated in a Cap2-dependent manner. Microarray data also suggested that Cap2 is required to mobilize iron through multiple mechanisms; chiefly by activation of genes in three iron uptake pathways and repression of iron utilizing and iron storage genes. The expression of HAP2, HAP32, and HAP5, core components of the HAP regulatory complex was induced in a Cap2-dependent manner indicating a feed-forward loop. In a feed-back loop, Cap2 repressed the expression of Sfu1, a negative regulator of iron uptake genes. Cap2 was coimmunoprecipitated with Hap5 from cell extracts prepared from iron-deprivation conditions indicating an in vivo association. ChIP assays demonstrated Hap32-dependent recruitment of Hap5 to the promoters of FRP1 (Cap2-induced) and ACO1 (Cap2-repressed). Together our data indicates that the Cap2-HAP complex functions both as a positive and a negative regulator to maintain iron homeostasis in C. albicans.
Diabetes mellitus has become one of the most common chronic diseases, thereby posing a major challenge to global health. Characterized by high levels of blood glucose (hyperglycemia), diabetes usually results from a loss of insulin-producing β-cells in the pancreas, leading to a deficiency of insulin (type 1 diabetes), or loss of insulin sensitivity (type 2 diabetes). Both types of diabetes have serious secondary complications, such as microvascular abnormalities, cardiovascular dysfunction, and kidney failure. Various complex factors, such as genetic and environmental factors, are associated with the pathophysiology of diabetes. Over the past two decades, the role of small, single-stranded noncoding microRNAs in various metabolic disorders, especially diabetes mellitus and its complications, has gained widespread attention in the scientific community. Discovered first as an endogenous regulator of development in the nematode Caenorhabditis elegans, these small RNAs post-transcriptionally suppress mRNA target expression. In this review, we discuss the potential roles of different microRNAs in diabetes and diabetes-related complications.
A cellulase producing fungus Schizophyllum commune NAIMCC-F-03379 was isolated from decomposed leaf sample of Lantana camera. The nutritional components (wheat bran, magnesium sulphate and calcium chloride concentrations) and physical parameters (temperature and pH) were optimised by response surface methodology for enhanced cellulase production by S. commune NAIMCC-F-03379. The optimized medium contained: 1% (w/v) wheat bran, 0.3 g/L MgSO4, 0.8–1.0 g/L CaCl2, optimum temperature and pH were 25 °C and 5 respectively. Under optimum condition, 5.35-fold increase in CMCase and 6.62-fold increase in FPase activity was obtained as compared to un-optimized condition. Crude cellulase enzyme was subjected to different purification techniques and comparative evaluation of their efficiency was performed. The aqueous two-phase system using polyethylene glycol 8000/MnSO4 system showed maximum purification with 10.4-fold increase in activity, 79.5% yield and 0.5 partition coefficient. The cellulase enzyme obtained from S. commune NAIMCC-F-03379 has shown high stability i.e. more than 55% relative activity after 12 h of incubation over wide range of temperature (25–65 °C) and pH (3–10). The molecular weight of the cellulase enzyme was estimated as ~ 60 kDa by using sodium dodecyl sulphate-polyacrylamide electrophoresis (SDS-PAGE) and zymography. Km and Vmax value of cellulase on carboxy-methyl cellulose were obtained as 0.0909 mg/mL and 45.45 μmol/min mg respectively. Rice straw and wheat bran were subjected to hydrolysis using cellulase and cellulase–xylanase cocktail and analysed by thin layer chromatography and high performance liquid chromatography (HPLC). The HPLC analysis showed glucose concentration of 1.162 mg/mL after enzymatic hydrolysis of rice straw.Electronic supplementary materialThe online version of this article (10.1186/s13568-018-0696-y) contains supplementary material, which is available to authorized users.
Background Lactobacilli are gatekeepers of vaginal ecosystem impeding growth of pathogenic microbes and their diversity varies across populations worldwide. The present study investigated diversity of human vaginal microbiota among females of Northeast India, who are distinct in dietary habits, lifestyle, and genomic composition from rest of India. Results Altogether, 154 bacterial isolates were obtained from vaginal swab samples of 40 pregnant and 29 non-pregnant females. The samples were sequenced for 16 s rRNA gene and analysed for identification using a dual approach of homology search and maximum likelihood based clustering. Molecular identification based on 16S rRNA gene sequence confirmed the isolates belonging to 31 species. Lactobacilli constituted 37.7% of the bacterial isolates with 10 species and other Lactic Acid Bacteria (39.61%) represented another 10 species, some of which are opportunistic pathogens. The remaining of the communities are mostly dominated by species of Staphylococcus (14.28%) and rarely by Propionibacterium avidum (3.90%) , Bacillus subtilis, Escherchia coli, Janthinobacterium lividum, and Kocuria kristinae (each 0.64%). Interestingly Lactobacillus mucosae and Enterococcus faecalis, which are globally uncommon vaginal microbes is found dominant among women of Northeast India. This tentatively reflects adaptability of particular Lactobacillus species, in distinct population, to better compete for receptors and nutrients in vaginal epithelium than other species. Further, intrageneric 16S rRNA gene exchange was observed among Enterococcus, Staphylococcus , and two species of Lactobacillus , and deep intraspecies divergence among L. mucosae, which pinpointed possibility of emergence of new strains with evolved functionality. Lactobacilli percentage decreased from young pregnant to aged non-pregnant women with maximum colonization in trimester II. Conclusion The study highlighted importance of assessment of vaginal microbiota, Lactobacillus in particular, across different population to gain more insight on female health. Electronic supplementary material The online version of this article (10.1186/s12866-019-1568-6) contains supplementary material, which is available to authorized users.
An elevated level of homocysteine (Hcy) leads to hyperhomocysteinemia (HHcy), which results in vascular dysfunction and pathological conditions identical to stroke symptoms. Hcy increases oxidative stress and leads to increase in blood-brain barrier permeability and leakage. Hydrogen sulfide (H S) production during the metabolism of Hcy has a cerebroprotective effect, although its effectiveness in Hcy-induced neurodegeneration and neurovascular permeability is less explored. Therefore, the current study was designed to perceive the neuroprotective effect of exogenous H S against HHcy, a cause of neurodegeneration. To test this hypothesis, we used four groups of mice: control, Hcy, control + sodium hydrosulfide hydrate (NaHS), and Hcy + NaHS, and an HHcy mice model in Swiss albino mice by giving a dose of 1.8 g of dl-Hcy/L in drinking for 8-10 weeks. Mice that have 30 µmol/L Hcy were taken for the study, and a H S supplementation of 20 μmol/L was given for 8 weeks to all groups of mice. HHcy results in the rise of the levels of superoxide and nitrite, although a concomitant decrease in the level of superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione, and arginase in oxidative stress and a concomitant decrease in the endogenous level of H S. Although H S supplementation ameliorated, the effect of HHcy and the levels of H S returned to the average level in HHcy animals supplemented with H S. Interestingly, H S supplementation ameliorated neurovascular remodeling and neurodegeneration. Thus, our study suggested that H S could be a beneficial therapeutic candidate for the treatment of Hcy-associated neurodegeneration, such as stroke and neurovascular disorders.
The vaginal microbial composition of wellbeing women were predominated by Lactobacillus group which play prime character in health-promoting activities including the prevention of the colonization of pathogenic microbe. The present study focused to characterize the probiotic and cytotoxicity potential of the Lactobacillus strains collected from the vaginal environment of the healthy women. Lactobacillus strains were identified via biochemical characterization and 16SrRNA gene sequencing. Strains were also evaluated for their probiotic potentials that includes antibiotics sensitivity; survivability to gastrointestinal conditions; antibacterial activities, biofilm production, auto aggregation and adhesion abilities to hydrocarbon. Cytotoxic activities were assessed through 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay using HeLa (cervical), AGS (gastric cancer) and A549 (lung cancer) cell lines. Results identified five bacterial strains viz., (Lactobacillus mucosae K76, L. fermentum K81, L. fermentum K85, L. reuteri K97 and L. reuteri K99) contains high probiotic potential and three strains with high cytotoxic activities against cancer cell lines can be further explodes for the human beneficial activities. Finding from this study also indicates that vaginal environment represents a novel source of probiotic candidates.
Chickpea wilt, caused by Fusarium oxysporum f. sp. ciceris, is a disease that decreases chickpea productivity and quality and can reduce its yield by as much as 15%. A newly isolated, moss rhizoid-associated Pseudomonas aeruginosa strain A7, demonstrated strong inhibition of Fusarium oxysporum f. sp. ciceris growth. An in vitro antimicrobial assay revealed A7 to suppress the growth of several fungal and bacterial plant pathogens by secreting secondary metabolites and by producing volatile compounds. In an in vivo pot experiment with Fusarium wilt infection in chickpea, the antagonist A7 exhibited a disease reduction by 77 ± 1.5%, and significantly reduced the disease incidence and severity indexes. Furthermore, A7 promoted chickpea growth in terms of root and shoot length and dry biomass during pot assay. The strain exhibited several traits associated with plant growth promotion, extracellular enzymatic production, and stress tolerance. Under aluminum stress conditions, in vitro growth of chickpea plants by A7 resulted in a significant increase in root length and plant biomass production. Additionally, hallmark genes for antibiotics production were identified in A7. The methanol extract of strain A7 demonstrated antimicrobial activity, leading to the identification of various antimicrobial compounds based on retention time and molecular weight. These findings strongly suggest that the strain’s significant biocontrol potential and plant growth enhancement could be a potential environmentally friendly process in agricultural crop production.
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