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 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 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 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

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 ◽  
...  
Keyword(s):  
Metal Ion ◽  
Ion Homeostasis ◽  
Cadmium Stress ◽  
Antioxidative Systems ◽  
Metal Ion Homeostasis

scholarly journals Amino Acid Features of PIB-ATPase Heavy Metal Transporters Enabling small Numbers of Organisms to Cope with Heavy Metal Pollution

2011 ◽  
Vol 5 ◽  
pp. BBI.S6206 ◽  
Author(s):  
E. Ashrafi ◽  
A. Alemzadeh ◽  
M. Ebrahimi ◽  
E. Ebrahimie ◽  
N. Dadkhodaei ◽  
...  
Keyword(s):  
Heavy Metal ◽  
Metal Ion ◽  
Ion Homeostasis ◽  
Structural Features ◽  
Site Directed Mutagenesis ◽  
Structural Protein ◽  
Tertiary Structures ◽  
Metal Transporters ◽  
Metal Ion Homeostasis ◽  
Wide Range

Phytoremediation refers to the use of plants for extraction and detoxification of pollutants, providing a new and powerful weapon against a polluted environment. In some plants, such as Thlaspi spp, heavy metal ATPases are involved in overall metal ion homeostasis and hyperaccumulation. P1B-ATPases pump a wide range of cations, especially heavy metals, across membranes against their electrochemical gradients. Determination of the protein characteristics of P1B-ATPases in hyperaccumulator plants provides a new opportuntity for engineering of phytoremediating plants. In this study, using diverse weighting and modeling approaches, 2644 protein characteristics of primary, secondary, and tertiary structures of P1B-ATPases in hyperaccumulator and nonhyperaccumulator plants were extracted and compared to identify differences between proteins in hyperaccumulator and nonhyperaccumulator pumps. Although the protein characteristics were variable in their weighting, tree and rule induction models; glycine count, frequency of glutamine-valine, and valine-phenylalanine count were the most important attributes highlighted by 10, five, and four models, respectively. In addition, a precise model was built to discriminate P1B-ATPases in different organisms based on their structural protein features. Moreover, reliable models for prediction of the hyperaccumulating activity of unknown P1B-ATPase pumps were developed. Uncovering important structural features of hyperaccumulator pumps in this study has provided the knowledge required for future modification and engineering of these pumps by techniques such as site-directed mutagenesis.

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

2021 ◽  
Author(s):  
Arjun Sukumaran ◽  
Samanta Pladwig ◽  
Jennifer 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 2,380 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 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 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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