Antioxidative systems, metal ion homeostasis and cadmium distribution in Iris lactea exposed to cadmium stress

2017 ◽  
Vol 139 ◽  
pp. 50-55 ◽  
Author(s):  
Qiang Guo ◽  
Lin Meng ◽  
Ya-Nan Zhang ◽  
Pei-Chun Mao ◽  
Xiao-Xia Tian ◽  
...  
2020 ◽  
Author(s):  
Saleh F. Alquethamy ◽  
Felise G. Adams ◽  
Ram Maharjan ◽  
Natasha N. Delgado ◽  
Maoge Zang ◽  
...  

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.


2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Stephanie L. Neville ◽  
Bart A. Eijkelkamp ◽  
Amber Lothian ◽  
James C. Paton ◽  
Blaine R. Roberts ◽  
...  

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.


Author(s):  
Saleh F. Alquethamy ◽  
Felise G. Adams ◽  
Ram Maharjan ◽  
Natasha N. Delgado ◽  
Maoge Zang ◽  
...  

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.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
A. Sukumaran ◽  
S. Pladwig ◽  
J. Geddes-McAlister

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.


2003 ◽  
Vol 18 (3) ◽  
pp. 162-169 ◽  
Author(s):  
S.E. Theocharis ◽  
A.P. Margeli ◽  
A. Koutselinis

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.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Rute Oliveira ◽  
Matthew J. Bush ◽  
Sílvia Pires ◽  
Govind Chandra ◽  
Delia Casas-Pastor ◽  
...  

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.


2006 ◽  
Vol 1 ◽  
pp. 117727190600100 ◽  
Author(s):  
Allan Evald Nielsen ◽  
Adam Bohr ◽  
Milena Penkowa

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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