scholarly journals Suppression and Activation of Intracellular Immune Response in Initial Severe Acute Respiratory Syndrome Coronavirus 2 Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
Lijia Jia ◽  
Zhen Chen ◽  
Yecheng Zhang ◽  
Li Ma ◽  
Liying Wang ◽  
...  
Keyword(s):  
Immune Response ◽  
Severe Acute Respiratory Syndrome ◽  
Metal Ion ◽  
Expression Profiles ◽  
Ion Homeostasis ◽  
Host Immune Response ◽  
Early Infection ◽  
Lag Phase ◽  
Two Stage ◽  
Metal Ion Homeostasis

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently the most important emerging pathogen worldwide, but its early transcriptional dynamics and host immune response remain unclear. Herein, the expression profiles of viral interactions with different types of hosts were comprehensively dissected to shed light on the early infection strategy of SARS-CoV-2 and the host immune response against infection. SARS-CoV-2 was found to exhibit a two-stage transcriptional strategy within the first 24 h of infection, comprising a lag phase that ends with the virus being paused and a log phase that starts when the viral load increases rapidly. Interestingly, the host innate immune response was found not to be activated (latent period) until the virus entered the log stage. Noteworthy, when intracellular immunity is suppressed, SARS-CoV-2 shows a correlation with dysregulation of metal ion homeostasis. Herein, the inhibitory activity of copper ions against SARS-CoV-2 was further validated in in vitro experiments. Coronavirus disease 2019-related genes (including CD38, PTX3, and TCN1) were also identified, which may serve as candidate host-restricted factors for interventional therapy. Collectively, these results confirm that the two-stage strategy of SARS-CoV-2 effectively aids its survival in early infection by regulating the host intracellular immunity, highlighting the key role of interferon in viral infection and potential therapeutic candidates for further investigations on antiviral strategies.

scholarly journals Comparing Transcriptome Profiles of Saccharomyces Cerevisiae Cells Exposed to Cadmium Selenide/Zinc Sulfide and Indium Phosphide/Zinc Sulfide

Genes ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 428
Author(s):  
Cullen Horstmann ◽  
Kyoungtae Kim
Keyword(s):  
Gene Expression ◽  
Zinc Sulfide ◽  
Metal Ion ◽  
Expression Profiles ◽  
Ion Homeostasis ◽  
Nitrogen Compound ◽  
Transmembrane Transport ◽  
Metabolic Processes ◽  
Mechanisms Of Toxicity ◽  
Metal Ion Homeostasis

The primary focus of our research was to obtain global gene expression data in baker’s yeast exposed to sub-lethal doses of quantum dots (QDs), such as green-emitting CdSe/ZnS and InP/ZnS, to reveal novel insights on their unique mechanisms of toxicity. Despite their promising applications, their toxicity and long-lasting effects on the environment are not well understood. To assess toxicity, we conducted cell viability assays, ROS detection assays, and assessed their effects on the trafficking of Vps10-GFP toward the trans-Golgi network with confocal microscopy. Most notably, we used RNA-sequencing (RNA-seq) to obtain gene expression profiles and gene identities of differentially expressed genes (DEGs) in QD-treated yeast. We found CdSe/ZnS QDs significantly altered genes implicated in carboxylic acid, amino acid, nitrogen compounds, protein metabolic processes, transmembrane transport, cellular homeostasis, cell wall organization, translation, and ribosomal biogenesis. Additionally, we found InP/ZnS QDs to alter genes associated with oxidation-reduction, transmembrane transport, metal ion homeostasis, cellular component organization, translation, and protein and nitrogen compound metabolic processes. Interestingly, we observed an increase in reactive oxygen species (ROS) in CdSe/ZnS-treated cells and a decrease in ROS levels in InP/ZnS-treated cells. Nevertheless, we concluded that both QDs modestly contributed cytotoxic effects on the budding yeast.

scholarly journals Zinc limitation in Klebsiella pneumoniae profiled by quantitative proteomics influences transcriptional regulation and cation transporter-associated capsule production

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
A. Sukumaran ◽  
S. Pladwig ◽  
J. Geddes-McAlister
Keyword(s):  
Klebsiella Pneumoniae ◽  
Metal Ion ◽  
Ion Homeostasis ◽  
Cellular Protein ◽  
Pcr Analysis ◽  
Phenotypic Analysis ◽  
Metal Ion Homeostasis ◽  
Capsule Production ◽  
The Impact

Abstract Background Microbial organisms encounter a variety of environmental conditions, including changes to metal ion availability. Metal ions play an important role in many biological processes for growth and survival. As such, microbes alter their cellular protein levels and secretion patterns in adaptation to a changing environment. This study focuses on Klebsiella pneumoniae, an opportunistic bacterium responsible for nosocomial infections. By using K. pneumoniae, we aim to determine how a nutrient-limited environment (e.g., zinc depletion) modulates the cellular proteome and secretome of the bacterium. By testing virulence in vitro, we provide novel insight into bacterial responses to limited environments in the presence of the host. Results Analysis of intra- and extracellular changes identified 2380 proteins from the total cellular proteome (cell pellet) and 246 secreted proteins (supernatant). Specifically, HutC, a repressor of the histidine utilization operon, showed significantly increased abundance under zinc-replete conditions, which coincided with an expected reduction in expression of genes within the hut operon from our validating qRT-PCR analysis. Additionally, we characterized a putative cation transport regulator, ChaB that showed significantly higher abundance under zinc-replete vs. -limited conditions, suggesting a role in metal ion homeostasis. Phenotypic analysis of a chaB deletion strain demonstrated a reduction in capsule production, zinc-dependent growth and ion utilization, and reduced virulence when compared to the wild-type strain. Conclusions This is first study to comprehensively profile the impact of zinc availability on the proteome and secretome of K. pneumoniae and uncover a novel connection between zinc transport and capsule production in the bacterial system.

scholarly journals Metallothionein: A Multifunctional Protein from Toxicity to Cancer

2003 ◽  
Vol 18 (3) ◽  
pp. 162-169 ◽  
Author(s):  
S.E. Theocharis ◽  
A.P. Margeli ◽  
A. Koutselinis
Keyword(s):  
Cell Proliferation ◽  
Metal Ion ◽  
Defense Mechanisms ◽  
Ion Homeostasis ◽  
Low Molecular Weight ◽  
Multifunctional Protein ◽  
Metal Ion Homeostasis ◽  
Potential Marker ◽  
Proliferation And Apoptosis ◽  
Carcinogenic Process

The metallothionein (MT) family is a class of low molecular weight, intracellular and cysteine-rich proteins presenting high affinity for metal ions. Although the members of this family were discovered nearly 40 years ago, their functional significance remains obscure. Four major MT isoforms, MT-1, MT-2, MT-3 and MT-4, have been identified in mammals. MTs are involved in many pathophysiological processes such as metal ion homeostasis and detoxification, protection against oxidative damage, cell proliferation and apoptosis, chemoresistance and radiotherapy resistance. MT isoforms have been shown to be involved in several aspects of the carcinogenic process, cancer development and progression. MT expression has been implicated as a transient response to any form of stress or injury providing cytoprotective action. Although MT participates in the carcinogenic process, its use as a potential marker of tumor differentiation or cell proliferation, or as a predictor of poor prognosis remains unclear. In the present review the involvement of MT in defense mechanisms to toxicity and in carcinogenicity is discussed.

scholarly journals The novel ECF56 SigG1-RsfG system modulates morphological differentiation and metal-ion homeostasis in Streptomyces tsukubaensis

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Rute Oliveira ◽  
Matthew J. Bush ◽  
Sílvia Pires ◽  
Govind Chandra ◽  
Delia Casas-Pastor ◽  
...  
Keyword(s):  
Metal Ion ◽  
Ion Homeostasis ◽  
Morphological Differentiation ◽  
The Novel ◽  
Copper Trafficking ◽  
Streptomyces Tsukubaensis ◽  
Metal Ion Homeostasis ◽  
Σ Factor ◽  
Domain Organisation

AbstractExtracytoplasmic function (ECF) sigma factors are key transcriptional regulators that prokaryotes have evolved to respond to environmental challenges. Streptomyces tsukubaensis harbours 42 ECFs to reprogram stress-responsive gene expression. Among them, SigG1 features a minimal conserved ECF σ2–σ4 architecture and an additional C-terminal extension that encodes a SnoaL_2 domain, which is characteristic for ECF σ factors of group ECF56. Although proteins with such domain organisation are widely found among Actinobacteria, the functional role of ECFs with a fused SnoaL_2 domain remains unknown. Our results show that in addition to predicted self-regulatory intramolecular amino acid interactions between the SnoaL_2 domain and the ECF core, SigG1 activity is controlled by the cognate anti-sigma protein RsfG, encoded by a co-transcribed sigG1-neighbouring gene. Characterisation of ∆sigG1 and ∆rsfG strains combined with RNA-seq and ChIP-seq experiments, suggests the involvement of SigG1 in the morphological differentiation programme of S. tsukubaensis. SigG1 regulates the expression of alanine dehydrogenase, ald and the WhiB-like regulator, wblC required for differentiation, in addition to iron and copper trafficking systems. Overall, our work establishes a model in which the activity of a σ factor of group ECF56, regulates morphogenesis and metal-ions homeostasis during development to ensure the timely progression of multicellular differentiation.

scholarly journals The Balance between Life and Death of Cells: Roles of Metallothioneins

2006 ◽  
Vol 1 ◽  
pp. 117727190600100 ◽  
Author(s):  
Allan Evald Nielsen ◽  
Adam Bohr ◽  
Milena Penkowa
Keyword(s):  
Metal Ion ◽  
Molecular Mechanisms ◽  
Energy Levels ◽  
Ion Homeostasis ◽  
Cellular Survival ◽  
Life And Death ◽  
Cellular Energy ◽  
Metal Ion Homeostasis ◽  
Pathological Conditions ◽  
Cysteine Rich Protein

Metallothionein (MT) is a highly conserved, low-molecular-weight, cysteine-rich protein that occurs in 4 isoforms (MT-I to MT-IV), of which MT-I+II are the major and best characterized proteins. This review will focus on mammalian MT-I+II and their functional impact upon cellular survival and death, as seen in two rather contrasting pathological conditions: Neurodegeneration and neoplasms. MT-I+II have analogous functions including: 1) Antioxidant scavenging of reactive oxygen species (ROS); 2) Cytoprotection against degeneration and apoptosis; 3) Stimulation of cell growth and repair including angiogenesis/revascularization, activation of stem/progenitor cells, and neuroregeneration. Thereby, MT-I+II mediate neuroprotection, CNS restoration and clinical recovery during neurodegenerative disorders. Due to the promotion of cell survival, increased MT-I+II levels have been associated with poor tumor prognosis, although the data are less clear and direct causative roles of MT-I+II in oncogenesis remain to be identified. The MT-I+II molecular mechanisms of actions are not fully elucidated. However, their role in metal ion homeostasis might be fundamental in controlling Zn-dependent transcription factors, protein synthesis, cellular energy levels/metabolism and cell redox state. Here, the neuroprotective and regenerative functions of MT-I+II are reviewed, and the presumed link to oncogenesis is critically perused.

scholarly journals The SloR/Dlg Metalloregulator Modulates Streptococcus mutans Virulence Gene Expression

2006 ◽  
Vol 188 (14) ◽  
pp. 5033-5044 ◽  
Author(s):  
Elizabeth Rolerson ◽  
Adam Swick ◽  
Lindsay Newlon ◽  
Cameron Palmer ◽  
Yong Pan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Streptococcus Mutans ◽  
Metal Ion ◽  
Ion Homeostasis ◽  
Virulence Gene ◽  
Wild Type ◽  
Genetic Competence ◽  
Virulence Gene Expression ◽  
Metal Ion Homeostasis

ABSTRACT Metal ion availability in the human oral cavity plays a putative role in Streptococcus mutans virulence gene expression and in appropriate formation of the plaque biofilm. In this report, we present evidence that supports such a role for the DtxR-like SloR metalloregulator (called Dlg in our previous publications) in this oral pathogen. Specifically, the results of gel mobility shift assays revealed the sloABC, sloR, comDE, ropA, sod, and spaP promoters as targets of SloR binding. We confirmed differential expression of these genes in a GMS584 SloR-deficient mutant versus the UA159 wild-type progenitor by real-time semiquantitative reverse transcriptase PCR experiments. The results of additional expression studies support a role for SloR in S. mutans control of glucosyltransferases, glucan binding proteins, and genes relevant to antibiotic resistance. Phenotypic analysis of GMS584 revealed that it forms aberrant biofilms on an abiotic surface, is compromised for genetic competence, and demonstrates heightened incorporation of iron and manganese as well as resistance to oxidative stress compared to the wild type. Taken together, these findings support a role for SloR in S. mutans adherence, biofilm formation, genetic competence, metal ion homeostasis, oxidative stress tolerance, and antibiotic gene regulation, all of which contribute to S. mutans-induced disease.

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