scholarly journals Phagocytic predation by the fungivorous amoeba Protostelium aurantium targets metal ion and redox homeostasis

2019 ◽  
Author(s):  
Silvia Radosa ◽  
Jakob L. Sprague ◽  
Renáta Tóth ◽  
Thomas Wolf ◽  
Marcel Sprenger ◽  
...  
Keyword(s):  
Fungal Pathogen ◽  
Metal Ion ◽  
Redox Homeostasis ◽  
Intracellular Killing ◽  
Methionine Biosynthesis ◽  
Basic Tool ◽  
Transcriptional Responses ◽  
Gene Deletions ◽  
The Third ◽  
Phagocytic Killing

SummaryPredatory interactions among microbes are considered to be a major evolutionary driving force for biodiversity and the defense against phagocytic killing. The fungivorous amoeba Protostelium aurantium has a wide fungal food spectrum but strongly discriminates among major pathogenic members of the Saccharomycotina. While C. albicans is not recognized, C. glabrata is rapidly internalized, but remains undigested. Phagocytic killing and feeding by P. aurantium is highly effective for the third major fungal pathogen, C. parapsilosis. Here we show that the different prey patterns of the three yeasts were reflected by distinct transcriptional responses, indicating fungal copper and redox homeostasis as primary targets during intracellular killing of C. parapsilosis. Gene deletions in this fungus for the highly expressed copper exporter Crp1 and the peroxiredoxin Prx1 confirmed their role in copper and redox homeostasis, respectively and identified methionine biosynthesis as a ROS sensitive metabolic target during predation. Both, intact Cu export and redox homeostasis contributed to the survival of C. parapsilosis not only when encountering P. aurantium, but also in the presence of human macrophages. As both genes were found to be widely conserved within the entire Candida clade, our results suggest that they could be part of a basic tool-kit to survive phagocytic attacks by environmental predators.

scholarly journals Longer Ubiquinone Side Chains Contribute to Enhanced Farnesol Resistance in Yeasts

2020 ◽  
Vol 8 (11) ◽  
pp. 1641
Author(s):  
Ruvini U. Pathirana ◽  
Cory Boone ◽  
Kenneth W. Nickerson
Keyword(s):  
Candida Species ◽  
Fungal Pathogen ◽  
Growth Conditions ◽  
Transfer Reactions ◽  
Free Radical Scavengers ◽  
Side Chain ◽  
Side Chains ◽  
Radical Scavengers ◽  
Transcriptional Responses ◽  
Electron Carrier

Ubiquinones (UQ) are intrinsic lipid components of many membranes. Besides their role in electron-transfer reactions there is evidence for them acting as free radical scavengers, yet their other roles in biological systems have received little study. The dimorphic fungal pathogen Candida albicans secretes farnesol as both a virulence factor and a quorum-sensing molecule. Thus, we were intrigued by the presence of UQ9 isoprenologue in farnesol-producing Candida species while other members of this genera harbor UQ7 as their major electron carrier. We examined the effect of UQ side chain length in Saccharomyces cerevisiae and C. albicans with a view towards identifying the mechanisms by which C. albicans protects itself from the high levels of farnesol it secretes, levels that are toxic to many other fungi including S. cerevisiae. In this study, we identify UQ9 as the major UQ isoprenoid in C. albicans, regardless of growth conditions or cell morphology. A S. cerevisiae model yeast engineered to make UQ9 instead of UQ6 was 4–5 times more resistant to exogenous farnesol than the parent yeast and this resistance was accompanied by greatly reduced reactive oxygen species (ROS) production. The resistance provided by UQ9 is specific for farnesol in that it does not increase resistance to high salt (1M NaCl) or other oxidants (5 mM H2O2 or 1 mM menadione). Additionally, the protection provided by UQ9 appears to be structural rather than transcriptional; UQ9 does not alter key transcriptional responses to farnesol stress. Here, we propose a model in which the longer UQ side chains are more firmly embedded in the mitochondrial membrane making them harder to pry out, so that in the presence of farnesol they remain functional without producing excess ROS. C. albicans and Candida dubliniensis evolved to use UQ9 rather than UQ7 as in other Candida species or UQ6 as in S. cerevisiae. This adaptive mechanism highlights the significance of UQ side chains in farnesol production and resistance quite apart from being an electron carrier in the respiratory chain.

scholarly journals Nitric Oxide in Chemostat-Cultured Escherichia coli Is Sensed by Fnr and Other Global Regulators: Unaltered Methionine Biosynthesis Indicates Lack of S Nitrosation

2006 ◽  
Vol 189 (5) ◽  
pp. 1845-1855 ◽  
Author(s):  
Steven T. Pullan ◽  
Mark D. Gidley ◽  
Richard A. Jones ◽  
Jason Barrett ◽  
Tania M. Stevanin ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Escherichia Coli ◽  
Nitrosative Stress ◽  
Adaptive Responses ◽  
Methionine Biosynthesis ◽  
Transcriptional Responses ◽  
No Donor ◽  
Global Regulators ◽  
E Coli ◽  
Cellular Effects

ABSTRACT We previously elucidated the global transcriptional responses of Escherichia coli to the nitrosating agent S-nitrosoglutathione (GSNO) in both aerobic and anaerobic chemostats, demonstrated the expression of nitric oxide (NO)-protective mechanisms, and obtained evidence of critical thiol nitrosation. The present study was the first to examine the transcriptome of NO-exposed E. coli in a chemostat. Using identical conditions, we compared the GSNO stimulon with the stimulon of NO released from two NO donor compounds {3-[2-hydroxy-1-(1-methyl-ethyl)-2-nitrosohydrazino]-1-propanamine (NOC-5) and 3-(2-hydroxy-1-methyl-2-nitrosohydrazino)-N-methyl-1-propanamine (NOC-7)} simultaneously and demonstrated that there were marked differences in the transcriptional responses to these distinct nitrosative stresses. Exposure to NO did not induce met genes, suggesting that, unlike GSNO, NO does not elicit homocysteine S nitrosation and compensatory increases in methionine biosynthesis. After entry into cells, exogenous methionine provided protection from GSNO-mediated killing but not from NO-mediated killing. Anaerobic exposure to NO led to up-regulation of multiple Fnr-repressed genes and down-regulation of Fnr-activated genes, including nrfA, which encodes cytochrome c nitrite reductase, providing strong evidence that there is NO inactivation of Fnr. Other global regulators apparently affected by NO were IscR, Fur, SoxR, NsrR, and NorR. We tried to identify components of the NorR regulon by performing a microarray comparison of NO-exposed wild-type and norR mutant strains; only norVW, encoding the NO-detoxifying flavorubredoxin and its cognate reductase, were unambiguously identified. Mutation of norV or norR had no effect on E. coli survival in mouse macrophages. Thus, GSNO (a nitrosating agent) and NO have distinct cellular effects; NO more effectively interacts with global regulators that mediate adaptive responses to nitrosative stress but does not affect methionine requirements arising from homocysteine nitrosation.

Metal ion binding of the third and fourth domains of Slc11a1 in a model membrane

RSC Advances ◽  
2016 ◽  
Vol 6 (90) ◽  
pp. 87270-87272
Author(s):  
Haiyan Qi ◽  
Wanxia Tang ◽  
Liming Bai ◽  
Lidi Gao
Keyword(s):  
Metal Ions ◽  
Metal Ion ◽  
Model Membrane ◽  
Transmembrane Domains ◽  
Model Membranes ◽  
Differential Scanning Calorimetric ◽  
Ion Binding ◽  
Metal Ion Binding ◽  
The Third

In this paper, differential scanning calorimetric (DSC) experiments have shown that the ability of third and fourth transmembrane domains of Slc11a1 to perturb DMPC model membranes is affected by metal ions.

scholarly journals Diverse human astrocyte and microglial transcriptional responses to Alzheimer’s pathology

2021 ◽  
Author(s):  
Amy M. Smith ◽  
Karen Davey ◽  
Stergios Tsartsalis ◽  
Combiz Khozoie ◽  
Nurun Fancy ◽  
...  
Keyword(s):  
Metal Ion ◽  
Ion Homeostasis ◽  
Cell Types ◽  
Specific Gene ◽  
Cell Type ◽  
Transcriptional Responses ◽  
Metal Ion Homeostasis ◽  
Gene Sets ◽  
Alzheimer’S Pathology ◽  
And Control

AbstractTo better define roles that astrocytes and microglia play in Alzheimer’s disease (AD), we used single-nuclei RNA-sequencing to comprehensively characterise transcriptomes in astrocyte and microglia nuclei selectively enriched during isolation post-mortem from neuropathologically defined AD and control brains with a range of amyloid-beta and phospho-tau (pTau) pathology. Significant differences in glial gene expression (including AD risk genes expressed in both the astrocytes [CLU, MEF2C, IQCK] and microglia [APOE, MS4A6A, PILRA]) were correlated with tissue amyloid or pTau expression. The differentially expressed genes were distinct between with the two cell types and pathologies, although common (but cell-type specific) gene sets were enriched with both pathologies in each cell type. Astrocytes showed enrichment for proteostatic, inflammatory and metal ion homeostasis pathways. Pathways for phagocytosis, inflammation and proteostasis were enriched in microglia and perivascular macrophages with greater tissue amyloid, but IL1-related pathway enrichment was found specifically in association with pTau. We also found distinguishable sub-clusters in the astrocytes and microglia characterised by transcriptional signatures related to either homeostatic functions or disease pathology. Gene co-expression analyses revealed potential functional associations of soluble biomarkers of AD in astrocytes (CLU) and microglia (GPNMB). Our work highlights responses of both astrocytes and microglia for pathological protein clearance and inflammation, as well as glial transcriptional diversity in AD.

scholarly journals Magnetic Field Induced Changes in the Shoot and Root Proteome of Barley (Hordeum vulgare L.)

2021 ◽  
Vol 12 ◽  
Author(s):  
Azita Shabrangy ◽  
Arindam Ghatak ◽  
Shuang Zhang ◽  
Alfred Priller ◽  
Palak Chaturvedi ◽  
...  
Keyword(s):  
Seed Germination ◽  
Metal Ion ◽  
Positive Impact ◽  
Germination Rate ◽  
Redox Homeostasis ◽  
Reduction Process ◽  
Plant Evolution ◽  
Metal Ion Binding ◽  
Hordeum Vulgare L ◽  
Root And Shoot Length

The geomagnetic field (GMF) has been present since the beginning of plant evolution. Recently, some researchers have focused their efforts on employing magnetic fields (MFs) higher than GMF to improve the seed germination, growth, and harvest of agriculturally important crop plants, as the use of MFs is an inexpensive and environment-friendly technique. In this study, we have employed different treatments of MF at 7 mT (milliTesla) at different time points of exposure, including 1, 3, and 6 h. The extended exposure was followed by five consecutive days at 6 h per day in barley seeds. The results showed a positive impact of MF on growth characteristics for 5-day-old seedlings, including seed germination rate, root and shoot length, and biomass weight. Furthermore, ~5 days of delay of flowering in pre-treated plants was also observed. We used a shotgun proteomics approach to identify changes in the protein signatures of root and shoot tissues under MF effects. In total, we have identified 2,896 proteins. Thirty-eight proteins in the shoot and 15 proteins in the root showed significant changes under the MF effect. Proteins involved in primary metabolic pathways were increased in contrast to proteins with a metal ion binding function, proteins that contain iron ions in their structure, and proteins involved in electron transfer chain, which were all decreased significantly in the treated tissues. The upregulated proteins' overall biological processes included carbohydrate metabolic process, oxidation-reduction process, and cell redox homeostasis, while down-regulated processes included translation and protein refolding. In general, shoot response was more affected by MF effect than root tissue, leading to the identification of 41 shoot specific proteins. This study provides an initial insight into the proteome regulation response to MF during barley's seedling stage.

scholarly journals PEGylated Liposome Encapsulation Increases the Lung Tissue Concentration of Vancomycin

2011 ◽  
Vol 55 (10) ◽  
pp. 4537-4542 ◽  
Author(s):  
Krishna Muppidi ◽  
Jeffrey Wang ◽  
Guru Betageri ◽  
Andrew S. Pumerantz
Keyword(s):  
Lung Tissue ◽  
Blood Circulation ◽  
Tissue Concentration ◽  
Kidney Tissue ◽  
Intracellular Killing ◽  
Content Type ◽  
Liposome Encapsulation ◽  
Phagocytic Killing ◽  
Vancomycin Treatment ◽  
Efficacy Of Treatment

ABSTRACTPneumonia due to methicillin-resistantStaphylococcus aureus(MRSA) often cannot be cured by vancomycin treatment. Poor lung tissue and intracellular penetration limits the ability to achieve effective bactericidal levels, particularly in alveolar macrophages, where MRSA can evade phagocytic killing. Compared to standard formulations, liposome encapsulation has been shown to enhance vancomycin intracellular killing of MRSA. In this murine pharmacokinetic and biodistribution study, PEGylated liposomal vancomycin, compared to standard and non-PEGylated formulations, significantly prolonged blood circulation time and increased deposition in lung, liver, and spleen and yet reduced accumulation in kidney tissue. As a result of optimizing antimicrobial targeting of infected lung tissue and limiting renal parenchymal exposure, administration of PEGylated liposomal vancomycin may improve the efficacy of treatment of MRSA pneumonia and reduce the risk of nephrotoxicity.

scholarly journals NADPH Oxidase Is Crucial for the Cellular Redox Homeostasis in Fungal Pathogen Botrytis cinerea

2019 ◽  
Vol 32 (11) ◽  
pp. 1508-1516
Author(s):  
Hua Li ◽  
Shiping Tian ◽  
Guozheng Qin
Keyword(s):  
Nadph Oxidase ◽  
Botrytis Cinerea ◽  
Fungal Pathogen ◽  
Molecular Mechanisms ◽  
Redox Homeostasis ◽  
Signal Transduction Pathway ◽  
Regulatory Subunit ◽  
Wild Type ◽  
Mutant Proteins ◽  
In The Wild

During interactions, both plants and pathogens produce reactive oxygen species (ROS). Plants generate ROS for defense induction, while pathogens synthesize ROS for growth, sporulation, and virulence. NADPH oxidase (NOX) complex in the plasma membrane represents a main protein complex for ROS production in pathogens. Although NOX plays a crucial role in pathogenicity of pathogens, the underlying molecular mechanisms of NOX, especially the proteins regulated by NOX, remain largely unknown. Here, we applied an iodoacetyl tandem mass tag-based redox proteomic assay to investigate the protein redox dynamics in deletion mutant of bcnoxR, which encodes a regulatory subunit of NOX in the fungal pathogen Botrytis cinerea. In total, 214 unique peptidyl cysteine (Cys) thiols from 168 proteins were identified and quantified in both the wild type and ∆bcnoxR mutant. The Cys thiols in the ∆bcnoxR mutant were generally more oxidized than those in the wild type, suggesting that BcNoxR is essential for maintaining the equilibrium of the redox state in B. cinerea. Site-specific thiol oxidation analysis indicated that 142 peptides containing the oxidized thiols changed abundance significantly in the ∆bcnoxR mutant. Proteins containing these differential peptides are classified into various functional categories. Functional analysis revealed that one of these proteins, 6-phosphate dehydrogenase, played roles in oxidative stress response and pathogenesis of B. cinerea. These results provide insight into the potential target proteins and the ROS signal transduction pathway regulated by NOX.

Metal ion-aromatic complexes. VI. Benzene .pi. complexes of metals of the third, fourth, and fifth groups

1968 ◽  
Vol 90 (21) ◽  
pp. 5941-5942 ◽  
Author(s):  
Th. Auel ◽  
E. L. Amma
Keyword(s):  
Metal Ion ◽  
The Third ◽  
Aromatic Complexes ◽  
Pi Complexes

scholarly journals Transcriptional Responses of Escherichia coli to S-Nitrosoglutathione under Defined Chemostat Conditions Reveal Major Changes in Methionine Biosynthesis

2005 ◽  
Vol 280 (11) ◽  
pp. 10065-10072 ◽  
Author(s):  
Janet Flatley ◽  
Jason Barrett ◽  
Steven T. Pullan ◽  
Martin N. Hughes ◽  
Jeffrey Green ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Methionine Biosynthesis ◽  
Transcriptional Responses

scholarly journals Modulation of the complex regulatory network for methionine biosynthesis in fungi

Genetics ◽  
2021 ◽  
Vol 217 (2) ◽  
Author(s):  
Manjari Shrivastava ◽  
Jinrong Feng ◽  
Mark Coles ◽  
Benjamin Clark ◽  
Amjad Islam ◽  
...  
Keyword(s):  
Filamentous Fungi ◽  
Fungal Pathogen ◽  
Biosynthetic Pathway ◽  
Protein A ◽  
Central Metabolism ◽  
Methionine Biosynthesis ◽  
Central Elements ◽  
Sulfur Containing ◽  
Complex Regulatory Network ◽  
Inorganic Sulfate

Abstract The assimilation of inorganic sulfate and the synthesis of the sulfur-containing amino acids methionine and cysteine is mediated by a multibranched biosynthetic pathway. We have investigated this circuitry in the fungal pathogen Candida albicans, which is phylogenetically intermediate between the filamentous fungi and Saccharomyces cerevisiae. In S. cerevisiae, this pathway is regulated by a collection of five transcription factors (Met4, Cbf1, Met28, and Met31/Met32), while in the filamentous fungi the pathway is controlled by a single Met4-like factor. We found that in C. albicans, the Met4 ortholog is also a core regulator of methionine biosynthesis, where it functions together with Cbf1. While C. albicans encodes this Met4 protein, a Met4 paralog designated Met28 (Orf19.7046), and a Met31 protein, deletion, and activation constructs suggest that of these proteins only Met4 is actually involved in the regulation of methionine biosynthesis. Both Met28 and Met31 are linked to other functions; Met28 appears essential, and Met32 appears implicated in the regulation of genes of central metabolism. Therefore, while S. cerevisiae and C. albicans share Cbf1 and Met4 as central elements of the methionine biosynthesis control, the other proteins that make up the circuit in S. cerevisiae are not members of the C. albicans control network, and so the S. cerevisiae circuit likely represents a recently evolved arrangement.

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