Arsenic Exposure Causes Global Changes in the Metalloproteome of Escherichia coli

Arsenic is a toxic metalloid with differential biological effects, depending on speciation and concentration. Trivalent arsenic (arsenite, AsIII) is more toxic at lower concentrations than the pentavalent form (arsenate, AsV). In E. coli, the proteins encoded by the arsRBC operon are the major arsenic detoxification mechanism. Our previous transcriptional analyses indicate broad changes in metal uptake and regulation upon arsenic exposure. Currently, it is not known how arsenic exposure impacts the cellular distribution of other metals. This study examines the metalloproteome of E. coli strains with and without the arsRBC operon in response to sublethal doses of AsIII and AsV. Size exclusion chromatography coupled with inductively coupled plasma mass spectrometry (SEC-ICPMS) was used to investigate the distribution of five metals (56Fe, 24Mg, 66Zn, 75As, and 63Cu) in proteins and protein complexes under native conditions. Parallel analysis by SEC-UV-Vis spectroscopy monitored the presence of protein cofactors. Together, these data reveal global changes in the metalloproteome, proteome, protein cofactors, and soluble intracellular metal pools in response to arsenic stress in E. coli. This work brings to light one outcome of metal exposure and suggests that metal toxicity on the cellular level arises from direct and indirect effects.

[1]  C. Rensing,et al.  As(III) Exposure Induces a Zinc Scarcity Response and Restricts Iron Uptake in High-Level Arsenic-Resistant Paenibacillus taichungensis Strain NC1 , 2022, Applied and environmental microbiology.

[2]  T. McDermott,et al.  Introducing the ArsR-Regulated Arsenic Stimulon , 2021, Frontiers in Microbiology.

[3]  F. Chen,et al.  Antagonistic effect of early stage zinc on arsenic toxicity induced preterm birth during pregnancy: evidence from a rural Bangladesh birth cohort , 2021, Chinese medical journal.

[4]  Milena S. Detzel,et al.  Heme Determination and Quantification Methods and Their Suita-bility for Practical Applications and Every-Day-Use. , 2020, Analytical chemistry.

[5]  V. Mehta,et al.  Structure and function of adenylyl cyclases, key enzymes in cellular signaling. , 2020, Current opinion in structural biology.

[6]  L. Lago,et al.  Choice of mobile phase: Implications for size exclusion chromatography-inductively coupled plasma-mass spectrometry analyses of copper, zinc and iron metalloproteins. , 2019, Journal of chromatography. A.

[7]  Zeling Xu,et al.  Zinc excess increases cellular demand for iron and decreases tolerance to copper in Escherichia coli , 2019, The Journal of Biological Chemistry.

[8]  T. McDermott,et al.  Transcriptomics analysis defines global cellular response of Agrobacterium tumefaciens 5A to arsenite exposure regulated through the histidine kinases PhoR and AioS. , 2019, Environmental microbiology.

[9]  B. Rosen,et al.  Pathways of arsenic uptake and efflux. , 2019, Environment international.

[10]  Gürol M. Süel,et al.  Magnesium Flux Modulates Ribosomes to Increase Bacterial Survival , 2019, Cell.

[11]  Ashkan Ojaghi,et al.  Deep UV dispersion and absorption spectroscopy of biomolecules. , 2019, Biomedical optics express.

[12]  Z. Deng,et al.  Genetic mechanisms of arsenic detoxification and metabolism in bacteria , 2018, Current Genetics.

[13]  Kaixiang Shi,et al.  Proteomics and genetic analyses reveal the effects of arsenite oxidation on metabolic pathways and the roles of AioR in Agrobacterium tumefaciens GW4. , 2018, Environmental pollution.

[14]  Damian J. Matuszewski,et al.  A comprehensive structural, biochemical and biological profiling of the human NUDIX hydrolase family , 2017, Nature Communications.

[15]  J. Helmann,et al.  Metal homeostasis and resistance in bacteria , 2017, Nature Reviews Microbiology.

[16]  A. Rehman,et al.  Proteomic analysis of an environmental isolate of Rhodotorula mucilaginosa after arsenic and cadmium challenge: Identification of a protein expression signature for heavy metal exposure. , 2016, Journal of proteomics.

[17]  F. Hartl,et al.  The GroEL-GroES Chaperonin Machine: A Nano-Cage for Protein Folding. , 2016, Trends in biochemical sciences.

[18]  M. Bansal,et al.  Protective Effects of Zinc Against Acute Arsenic Toxicity by Regulating Antioxidant Defense System and Cumulative Metallothionein Expression , 2016, Biological Trace Element Research.

[19]  S. Gygi,et al.  Proteomic Analysis Identifies Ribosome Reduction as an Effective Proteotoxic Stress Response* , 2015, The Journal of Biological Chemistry.

[20]  J. Andersen,et al.  Manganese disturbs metal and protein homeostasis in Caenorhabditis elegans. , 2014, Metallomics : integrated biometal science.

[21]  Seung-Do Yu,et al.  Environmental Source of Arsenic Exposure , 2014, Journal of preventive medicine and public health = Yebang Uihakhoe chi.

[22]  C. Masters,et al.  Profiling the iron, copper and zinc content in primary neuron and astrocyte cultures by rapid online quantitative size exclusion chromatography-inductively coupled plasma-mass spectrometry. , 2013, Metallomics : integrated biometal science.

[23]  H. Fu,et al.  Pathways of arsenic uptake and efflux. , 2019, Environment international.

[24]  B. Bothner,et al.  Integrated co-regulation of bacterial arsenic and phosphorus metabolisms. , 2012, Environmental microbiology.

[25]  G. Basturea,et al.  Growth of a Bacterium That Apparently Uses Arsenic Instead of Phosphorus Is a Consequence of Massive Ribosome Breakdown*♦ , 2012, The Journal of Biological Chemistry.

[26]  Guanghui Liu,et al.  A periplasmic arsenite-binding protein involved in regulating arsenite oxidation. , 2012, Environmental microbiology.

[27]  Jeffrey T. Rubino,et al.  Coordination chemistry of copper proteins: how nature handles a toxic cargo for essential function. , 2012, Journal of inorganic biochemistry.

[28]  T. McDermott,et al.  Genome Sequence of the Arsenite-Oxidizing Strain Agrobacterium tumefaciens 5A , 2012, Journal of bacteriology.

[29]  B. D. Beck,et al.  Arsenic exposure and toxicology: a historical perspective. , 2011, Toxicological sciences : an official journal of the Society of Toxicology.

[30]  L. Hudson,et al.  Arsenite Interacts Selectively with Zinc Finger Proteins Containing C3H1 or C4 Motifs* , 2011, The Journal of Biological Chemistry.

[31]  C. Saltikov,et al.  The ArsR Repressor Mediates Arsenite-Dependent Regulation of Arsenate Respiration and Detoxification Operons of Shewanella sp. Strain ANA-3 , 2009, Journal of bacteriology.

[32]  J. Tamames,et al.  Microbial responses to environmental arsenic , 2009, BioMetals.

[33]  Dietrich H. Nies,et al.  Glutathione and Transition-Metal Homeostasis in Escherichia coli , 2008, Journal of bacteriology.

[34]  S. Sambu,et al.  Arsenic in food and water – a brief history , 2008, Toxicology and industrial health.

[35]  D. Hassett,et al.  Complex Regulation of Arsenite Oxidation in Agrobacterium tumefaciens , 2006, Journal of bacteriology.

[36]  M. Massiah,et al.  Structures and mechanisms of Nudix hydrolases. , 2005, Archives of biochemistry and biophysics.

[37]  X. Le,et al.  Evidence of hemoglobin binding to arsenic as a basis for the accumulation of arsenic in rat blood. , 2004, Chemical research in toxicology.

[38]  B. Rosen,et al.  Biochemistry of arsenic detoxification , 2002, FEBS letters.

[39]  Fredrik Åslund,et al.  Reactivity of Glutaredoxins 1, 2, and 3 fromEscherichia coli Shows That Glutaredoxin 2 Is the Primary Hydrogen Donor to ArsC-catalyzed Arsenate Reduction* , 1999, The Journal of Biological Chemistry.

[40]  A. Albores,et al.  Arsenite alters heme synthesis in long-term cultures of adult rat hepatocytes. , 1999, Toxicological sciences : an official journal of the Society of Toxicology.

[41]  P. Macheroux,et al.  UV-visible spectroscopy as a tool to study flavoproteins. , 1999, Methods in molecular biology.

[42]  B. Rosen,et al.  The ars operon of Escherichia coli confers arsenical and antimonial resistance , 1995, Journal of bacteriology.

[43]  H. Aposhian,et al.  Arsenic binding proteins of mammalian systems: I. Isolation of three arsenite-binding proteins of rabbit liver. , 1994, Toxicology.

[44]  M. Steer.  Adenyl Cyclase , 1975, Annals of surgery.