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 Transition Metal Ion Homeostasis

2016 ◽  
pp. 171-220
Author(s):  
Jessica R. Sheldon ◽  
Ronald S. Flannagan ◽  
Mélissa Hannauer ◽  
David E. Heinrichs
Keyword(s):  
Transition Metal ◽  
Metal Ion ◽  
Ion Homeostasis ◽  
Transition Metal Ion ◽  
Metal Ion Homeostasis

scholarly journals The molecular basis of Acinetobacter baumannii cadmium toxicity and resistance

2020 ◽  
Author(s):  
Saleh F. Alquethamy ◽  
Felise G. Adams ◽  
Ram Maharjan ◽  
Natasha N. Delgado ◽  
Maoge Zang ◽  
...  
Keyword(s):  
Heavy Metal ◽  
Acinetobacter Baumannii ◽  
Metal Ion ◽  
Cadmium Toxicity ◽  
Ion Homeostasis ◽  
Cadmium Stress ◽  
Primary Role ◽  
Metal Ion Homeostasis ◽  
Primary Means ◽  
The Impact

ABSTRACTAcinetobacter species are ubiquitous Gram-negative bacteria that can be found in water, soil and as commensals of the human skin. The successful inhabitation of Acinetobacter species in diverse environments is primarily attributable to the expression of an arsenal of stress resistance determinants, which includes an extensive repertoire of metal ion efflux systems. Although metal ion homeostasis in the hospital pathogen Acinetobacter baumannii is known to contribute to pathogenesis, insights into its metal ion transporters for environmental persistence are lacking. Here, we studied the impact of cadmium stress on A. baumannii. Our functional genomics and independent mutant analyses revealed a primary role for CzcE, a member of the cation diffusion facilitator (CDF) superfamily, in resisting cadmium stress. Further, we show that the CzcCBA heavy metal efflux system also contributes to cadmium efflux. Analysis of the A. baumannii metallome under cadmium stress showed zinc depletion and copper enrichment, which are likely to influence cellular fitness. Overall, this work expands our understanding of the role of membrane transporters in A. baumannii metal ion homeostasis.IMPORTANCECadmium toxicity is a widespread problem, yet the interaction of this heavy metal with biological systems is poorly understood. Some microbes have evolved traits to proactively counteract cadmium toxicity, which includes Acinetobacter baumannii. Here we show that A. baumannii utilises a dedicated cadmium efflux protein in concert with a system that is primarily attuned to zinc efflux, to efficiently overcome cadmium stress. The molecular characterization of A. baumannii under cadmium stress revealed how active cadmium efflux plays a key role in preventing the dysregulation of bacterial metal ion homeostasis, which appeared to be the primary means by which cadmium exerts toxicity upon the bacterium.

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 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 The molecular basis of Acinetobacter baumannii cadmium toxicity and resistance

2021 ◽  
Author(s):  
Saleh F. Alquethamy ◽  
Felise G. Adams ◽  
Ram Maharjan ◽  
Natasha N. Delgado ◽  
Maoge Zang ◽  
...  
Keyword(s):  
Heavy Metal ◽  
Acinetobacter Baumannii ◽  
Metal Ion ◽  
Cadmium Toxicity ◽  
Ion Homeostasis ◽  
Cadmium Stress ◽  
Primary Role ◽  
Metal Ion Homeostasis ◽  
Primary Means ◽  
The Impact

Acinetobacter species are ubiquitous Gram-negative bacteria that can be found in water, soil, and as commensals of the human skin. The successful inhabitation of Acinetobacter species in diverse environments is primarily attributable to the expression of an arsenal of stress resistance determinants, which includes an extensive repertoire of metal ion efflux systems. Metal ion homeostasis in the hospital pathogen Acinetobacter baumannii contributes to pathogenesis, however, insights into its metal ion transporters for environmental persistence are lacking. Here, we studied the impact of cadmium stress on A. baumannii . Our functional genomics and independent mutant analyses revealed a primary role for CzcE, a member of the cation diffusion facilitator (CDF) superfamily, in resisting cadmium stress. We also show that the CzcCBA heavy metal efflux system contributes to cadmium efflux. Collectively, these systems provide A. baumannii with a comprehensive cadmium translocation pathway from the cytoplasm to the periplasm and subsequently the extracellular space. Furthermore, analysis of the A. baumannii metallome under cadmium stress showed zinc depletion, as well as copper enrichment, which are likely to influence cellular fitness. Overall, this work provides new knowledge on the role of a broad arsenal of membrane transporters in A. baumannii metal ion homeostasis. IMPORTANCE Cadmium toxicity is a widespread problem, yet the interaction of this heavy metal with biological systems is poorly understood. Some microbes have evolved traits to proactively counteract cadmium toxicity, including Acinetobacter baumannii , which is notorious for persisting in harsh environments. Here we show that A. baumannii utilises a dedicated cadmium efflux protein in concert with a system that is primarily attuned to zinc efflux to efficiently overcome cadmium stress. The molecular characterization of A. baumannii under cadmium stress revealed how active cadmium efflux plays a key role in preventing the dysregulation of bacterial metal ion homeostasis, which appeared to be a primary means by which cadmium exerts toxicity upon the bacterium.

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.

Transition-metal ion-mediated morphological transformation of pyridine-based peptide nanostructures

2021 ◽  
Vol 45 (1) ◽  
pp. 153-161
Author(s):  
Narendra Singh ◽  
Ramesh Singh ◽  
Swati Sharma ◽  
Khushboo Kesharwani ◽  
Khashti Ballabh Joshi ◽  
...  
Keyword(s):  
Transition Metal ◽  
Metal Ion ◽  
Chemical Structure ◽  
Morphological Transformation ◽  
Transition Metal Ion

Pyridine-mediated constitutionally isomeric artificial metallopeptides possess remarkable advantages over the natural counterparts mainly due to their tailor-made chemical structure.

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.

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