scholarly journals Streptococcus pneumoniae metal homeostasis alters cellular metabolism

Metallomics ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 1416-1427 ◽  
Author(s):  
Lindsey R. Burcham ◽  
Rebecca A. Hill ◽  
Rachel C. Caulkins ◽  
Joseph P. Emerson ◽  
Bindu Nanduri ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Metal Ion ◽  
Genetic Locus ◽  
Ion Homeostasis ◽  
Cellular Metabolism ◽  
Metal Homeostasis ◽  
Central Metabolism ◽  
Human Pathogen ◽  
Metal Ion Homeostasis

Through parallel metabolomics and proteomics, we identified a previously uncharacterized genetic locus that contributes to metal ion homeostasis and central metabolism in the human pathogen Streptococcus pneumoniae.

scholarly journals SP1433-1438 operon of Streptococcus pneumoniae regulates metal homeostasis and cellular metabolism during zinc-stress

2018 ◽  
Author(s):  
Lindsey R. Burcham ◽  
Rebecca A. Hill ◽  
Rachel C. Caulkins ◽  
Joseph P. Emerson ◽  
Bindu Nanduri ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Proteomic Analysis ◽  
Metal Ion ◽  
Ion Homeostasis ◽  
Acute Otitis Media ◽  
Cellular Metabolism ◽  
Energy Coupling ◽  
Transport Systems ◽  
Pcr Analysis ◽  
Metal Ion Homeostasis

AbstractStreptococcus pneumoniae colonizes the mucosa of the human nasopharynx and is a leading cause of community-acquired pneumonia, acute otitis media, and bacterial meningitis. Metal ion homeostasis is vital to the survival of this pathogen and contributes significantly to both colonization and invasive disease. Microarray and qRT-PCR analysis revealed an upregulation of an uncharacterized operon (SP1433-1438) in pneumococci subjected to metal-chelation by N,N,N’,N’-tetrakis-(2-Pyridylmethyl)ethylenediamine (TPEN). Supplementation of either zinc or cobalt following TPEN treatment drastically abrogated induction. BLAST analysis predicted this operon to encode two ABC-transporters, sharing homology to a multidrug resistance system (SP1434-1435) and an energy-coupling factor (ECF) transport system (SP1436-1438). Inductively coupled plasma mass spectrometry (ICP-MS) analysis indicated changes in intracellular concentrations of iron, zinc, and manganese ions in a Δ1434-8 strain compared to parental T4R. Analysis of the secreted metabolomic profile of the T4R and Δ1434-8 strains identified significant changes in pneumococcal glycolytic pathways, indicating a shift towards increased production of acetate. Additionally, proteomic analysis revealed 41 differentially expressed proteins in the Δ1434-8 strain, with roughly 20% of them regulated by the global catabolite repressor, CcpA. Based on these findings, we propose that the SP1433-1438 operon is largely involved in the central metabolism of S. pneumoniae during zinc-limitation.ImportanceMetal sequestration is a common strategy utilized by the host immune response as well as antibiotics such as vancomycin to kill invading bacterial pathogens (1). However, pneumococcus is still able to thrive under zinc-limiting conditions. This study describes a previously uncharacterized operon encoding two ABC transport systems that are strongly induced during zinc-limiting conditions. This operon was found to be regulated by a zinc-dependent regulator (SP1433) that functions independently of the overarching AdcR regulon. We have additionally utilized a 2D-NMR approach to analyze the secreted metabolome and have employed proteomic analysis to identify a role for these systems in the maintenance of cellular metabolism. This study provides new information on how Streptococcus pneumoniae responds and adapts to zinc-limiting conditions.

scholarly journals Dysregulation of transition metal ion homeostasis is the molecular basis for cadmium toxicity in Streptococcus pneumoniae

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Stephanie L. Begg ◽  
Bart A. Eijkelkamp ◽  
Zhenyao Luo ◽  
Rafael M. Couñago ◽  
Jacqueline R. Morey ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Transition Metal ◽  
Molecular Basis ◽  
Metal Ion ◽  
Cadmium Toxicity ◽  
Ion Homeostasis ◽  
Transition Metal Ion ◽  
Metal Ion Homeostasis

scholarly journals Cadmium stress dictates central carbon flux and alters membrane composition in Streptococcus pneumoniae

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Stephanie L. Neville ◽  
Bart A. Eijkelkamp ◽  
Amber Lothian ◽  
James C. Paton ◽  
Blaine R. Roberts ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Metal Ion ◽  
Lipid Membrane ◽  
Ion Homeostasis ◽  
Cadmium Stress ◽  
Pentose Phosphate ◽  
Membrane Composition ◽  
Metal Ion Homeostasis ◽  
Central Carbon ◽  
Cellular Pathways

AbstractMetal ion homeostasis is essential for all forms of life. However, the breadth of intracellular impacts that arise upon dysregulation of metal ion homeostasis remain to be elucidated. Here, we used cadmium, a non-physiological metal ion, to investigate how the bacterial pathogen, Streptococcus pneumoniae, resists metal ion stress and dyshomeostasis. By combining transcriptomics, metabolomics and metalloproteomics, we reveal that cadmium stress dysregulates numerous essential cellular pathways including central carbon metabolism, lipid membrane biogenesis and homeostasis, and capsule production at the transcriptional and/or functional level. Despite the breadth of cellular pathways susceptible to metal intoxication, we show that S. pneumoniae is able to maintain viability by utilizing cellular pathways that are predominately metal-independent, such as the pentose phosphate pathway to maintain energy production. Collectively, this work provides insight into the cellular processes impacted by cadmium and how resistance to metal ion toxicity is achieved in S. pneumoniae.

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.

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