An ion for an iron: streptococcal metal homeostasis under oxidative stress

2019 ◽  
Vol 476 (4) ◽  
pp. 699-703
Author(s):  
Nicholas S. Jakubovics
Keyword(s):  
Oxidative Stress ◽  
Superoxide Dismutase ◽  
Metal Ion ◽  
Molecular Genetic ◽  
Ion Homeostasis ◽  
Fold Increase ◽  
System Component ◽  
Bacterial Cells ◽  
Holistic View ◽  
Metal Ion Homeostasis

Abstract The ability of opportunistic pathogens such as Group A Streptococcus (GAS) to transition between mucosal colonisation and invasive disease requires complex systems for adapting to markedly different host environments. The battle to acquire essential trace metals such as manganese and iron from the host is central to pathogenesis. Using a molecular genetic approach, Turner et al. [Biochem. J. (2019) 476, 595–611] show that it is not just individual metal concentrations that are important, but the ratio of iron to manganese within cells. Increasing this ratio by knocking out pmtA, encoding the Fe(II) exporter PmtA, or by disrupting mtsA, encoding an MtsABC Mn(II)-import system component, led to reductions in superoxide dismutase (SodA) activity and increased sensitivity to oxidative stress. The authors show that SodA is at least 4-fold more active with Mn bound than with Fe and speculate that high intracellular Fe:Mn ratios reduce superoxide dismutase activity through the mismetalation of SodA. Challenging wild-type GAS with 1 mM H2O2 led to a decrease in Fe:Mn ratio and a 3-fold increase in SodA activity, indicating that modulation of the balance between intracellular Fe and Mn may play an important role in adaptation to oxidative stress. This work unravels some of the key mechanisms for maintaining appropriate Mn and Fe concentrations within bacterial cells and underscores the need for future studies that take an holistic view to metal ion homeostasis in bacteria. Strategies aimed at interfering with the balance of intracellular metal ions represent a promising approach for the control of invasive microbial infections.

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.

scholarly journals A secreted fungal histidine‐ and alanine‐rich protein regulates metal ion homeostasis and oxidative stress

2020 ◽  
Vol 227 (4) ◽  
pp. 1174-1188 ◽  
Author(s):  
Robin Nostadt ◽  
Magdalena Hilbert ◽  
Shadab Nizam ◽  
Hanna Rovenich ◽  
Stephan Wawra ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Metal Ion ◽  
Ion Homeostasis ◽  
Metal Ion Homeostasis ◽  
And Oxidative Stress

scholarly journals Erythrocytes as Biomarkers of Virus and Bacteria in View of Metal Ion Homeostasis

2021 ◽  
Author(s):  
Erland Johansson ◽  
Anders B. Falk
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Metal Ion ◽  
Technological Development ◽  
Purinergic Signaling ◽  
Genetic Diseases ◽  
Ion Homeostasis ◽  
Proper Function ◽  
Healthy Controls ◽  
Metal Ion Homeostasis

The erythrocyte contributes to the immune system in several ways. It sequesters interferons, interleukins or chemokines and by binding nucleic acid. It binds virus and bacteria and may deliver bacteria to macrophages for phagocytosis. It may also kill bacteria directly with oxygen. For proper function of the erythrocyte, homeostasis of reactive oxygen species, selenium, metal ions and trace elements is important. Erythrocytes display morphological and metabolic changes in diseases like sepsis, and in several genetic diseases. Patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), giving rise to the coronavirus disease 2019 (Covid-19), show many erythrocyte changes as compared to healthy controls. The erythrocyte responds to hemolysins by purinergic signaling leading to hemolysis or phosphatidylserine exposure on the plasma membrane. Phosphatidylserine marks erythrocytes for clearance by spleen macrophages. Regulated erythrocyte cell death, also called eryptosis, can be induced by oxidative stress, pathogen infection, and certain diseases like sepsis. Erythrocytes may, in the future, contribute more to diagnosis based on research and diagnostic technological development.

scholarly journals Neurotoxicity Linked to Dysfunctional Metal Ion Homeostasis and Xenobiotic Metal Exposure: Redox Signaling and Oxidative Stress

2018 ◽  
Vol 28 (18) ◽  
pp. 1669-1703 ◽  
Author(s):  
Carla Garza-Lombó ◽  
Yanahi Posadas ◽  
Liliana Quintanar ◽  
María E. Gonsebatt ◽  
Rodrigo Franco
Keyword(s):  
Oxidative Stress ◽  
Metal Ion ◽  
Ion Homeostasis ◽  
Redox Signaling ◽  
Metal Exposure ◽  
Metal Ion Homeostasis ◽  
And Oxidative Stress

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 Identification by RNA Profiling and Mutational Analysis of the Novel Copper Resistance Determinants CrdA (HP1326), CrdB (HP1327), and CzcB (HP1328) in Helicobacter pylori

2002 ◽  
Vol 184 (23) ◽  
pp. 6700-6708 ◽  
Author(s):  
Barbara Waidner ◽  
Klaus Melchers ◽  
Igor Ivanov ◽  
Hannes Loferer ◽  
Klaus W. Bensch ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Metal Ion ◽  
Specific Protein ◽  
Copper Resistance ◽  
System Component ◽  
The Novel ◽  
Rna Profiling ◽  
Metal Ion Homeostasis ◽  
Resistance Determinants ◽  
H Pylori

ABSTRACT Mechanisms involved in maintaining cytoplasmic metal ion homeostasis play a central role in the adaptation of Helicobacter pylori to the changing gastric environment. An investigation of the global regulatory responses to copper ions by using RNA profiling with a threshold factor of 4.0 revealed that copper induces transcription of 19 H. pylori genes and that only the ferritin gene pfr is repressed. The 57-fold copper induction identified the HP1326 gene encoding an H. pylori-specific protein as a candidate for a novel copper resistance determinant. The HP1326 gene is expressed as a monocistronic unit, and two small HP1326 mRNAs are copper induced. The HP1326 protein is secreted and is required for copper resistance maintained by cytoplasmic copper homeostasis, as H. pylori HP1326 mutants were copper sensitive and displayed increased copper induction of HP1326 transcription as well as elevated copper repression of ferritin synthesis. The clear copper-sensitive phenotype displayed by H. pylori HP1327 and HP1328 mutants provides strong evidence that the HP1326 protein, together with the signal peptide site of the H. pylori-specific protein HP1327, whose gene is located downstream from that encoding HP1326, and the CzcB and CzcA metal efflux system component homologs HP1328 and HP1329, constitutes a novel type of copper efflux pump, as discussed below. The HP1329 gene could not be inactivated, but the 14-fold transcriptional copper induction determined by RNA profiling points towards a function of the encoded CzcA homolog in copper resistance. In summary, results from RNA profiling identified the novel H. pylori-specific copper resistance determinants CrdA (HP1326) and CrdB (HP1327), which are required for adaptation to copper-rich environmental conditions.

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.

Sign in / Sign up

Export Citation Format

Share Document