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Zinc Toxicity and Iron-Sulfur Cluster Biogenesis in Escherichia coli

While zinc is an essential trace metal in biology, excess zinc is toxic to organisms. Previous studies have shown that zinc toxicity is associated with disruption of the [4Fe-4S] clusters in various dehydratases in Escherichia coli. Here, we report that the intracellular zinc overload in E. coli cel...

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Autores principales: Li, Jianghui, Ren, Xiaojun, Fan, Bingqian, Huang, Zhaoyang, Wang, Wu, Zhou, Huaibin, Lou, Zhefeng, Ding, Huangen, Lyu, Jianxin, Tan, Guoqiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6495748/
https://www.ncbi.nlm.nih.gov/pubmed/30824435
http://dx.doi.org/10.1128/AEM.01967-18
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author Li, Jianghui
Ren, Xiaojun
Fan, Bingqian
Huang, Zhaoyang
Wang, Wu
Zhou, Huaibin
Lou, Zhefeng
Ding, Huangen
Lyu, Jianxin
Tan, Guoqiang
author_facet Li, Jianghui
Ren, Xiaojun
Fan, Bingqian
Huang, Zhaoyang
Wang, Wu
Zhou, Huaibin
Lou, Zhefeng
Ding, Huangen
Lyu, Jianxin
Tan, Guoqiang
author_sort Li, Jianghui
collection PubMed
description While zinc is an essential trace metal in biology, excess zinc is toxic to organisms. Previous studies have shown that zinc toxicity is associated with disruption of the [4Fe-4S] clusters in various dehydratases in Escherichia coli. Here, we report that the intracellular zinc overload in E. coli cells inhibits iron-sulfur cluster biogenesis without affecting the preassembled iron-sulfur clusters in proteins. Among the housekeeping iron-sulfur cluster assembly proteins encoded by the gene cluster iscSUA-hscBA-fdx-iscX in E. coli cells, the scaffold IscU, the iron chaperone IscA, and ferredoxin have strong zinc binding activity in cells, suggesting that intracellular zinc overload inhibits iron-sulfur cluster biogenesis by binding to the iron-sulfur cluster assembly proteins. Mutations of the conserved cysteine residues to serine in IscA, IscU, or ferredoxin completely abolish the zinc binding activity of the proteins, indicating that zinc can compete with iron or iron-sulfur cluster binding in IscA, IscU, and ferredoxin and block iron-sulfur cluster biogenesis. Furthermore, intracellular zinc overload appears to emulate the slow-growth phenotype of the E. coli mutant cells with deletion of the iron-sulfur cluster assembly proteins IscU, IscA, and ferredoxin. Our results suggest that intracellular zinc overload inhibits iron-sulfur cluster biogenesis by targeting the iron-sulfur cluster assembly proteins IscU, IscA, and ferredoxin in E. coli cells. IMPORTANCE Zinc toxicity has been implicated in causing various human diseases. High concentrations of zinc can also inhibit bacterial cell growth. However, the underlying mechanism has not been fully understood. Here, we report that zinc overload in Escherichia coli cells inhibits iron-sulfur cluster biogenesis by targeting specific iron-sulfur cluster assembly proteins. Because iron-sulfur proteins are involved in diverse physiological processes, the zinc-mediated inhibition of iron-sulfur cluster biogenesis could be largely responsible for the zinc-mediated cytotoxicity. Our finding provides new insights on how intracellular zinc overload may inhibit cellular functions in bacteria.
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spelling pubmed-64957482019-05-16 Zinc Toxicity and Iron-Sulfur Cluster Biogenesis in Escherichia coli Li, Jianghui Ren, Xiaojun Fan, Bingqian Huang, Zhaoyang Wang, Wu Zhou, Huaibin Lou, Zhefeng Ding, Huangen Lyu, Jianxin Tan, Guoqiang Appl Environ Microbiol Environmental Microbiology While zinc is an essential trace metal in biology, excess zinc is toxic to organisms. Previous studies have shown that zinc toxicity is associated with disruption of the [4Fe-4S] clusters in various dehydratases in Escherichia coli. Here, we report that the intracellular zinc overload in E. coli cells inhibits iron-sulfur cluster biogenesis without affecting the preassembled iron-sulfur clusters in proteins. Among the housekeeping iron-sulfur cluster assembly proteins encoded by the gene cluster iscSUA-hscBA-fdx-iscX in E. coli cells, the scaffold IscU, the iron chaperone IscA, and ferredoxin have strong zinc binding activity in cells, suggesting that intracellular zinc overload inhibits iron-sulfur cluster biogenesis by binding to the iron-sulfur cluster assembly proteins. Mutations of the conserved cysteine residues to serine in IscA, IscU, or ferredoxin completely abolish the zinc binding activity of the proteins, indicating that zinc can compete with iron or iron-sulfur cluster binding in IscA, IscU, and ferredoxin and block iron-sulfur cluster biogenesis. Furthermore, intracellular zinc overload appears to emulate the slow-growth phenotype of the E. coli mutant cells with deletion of the iron-sulfur cluster assembly proteins IscU, IscA, and ferredoxin. Our results suggest that intracellular zinc overload inhibits iron-sulfur cluster biogenesis by targeting the iron-sulfur cluster assembly proteins IscU, IscA, and ferredoxin in E. coli cells. IMPORTANCE Zinc toxicity has been implicated in causing various human diseases. High concentrations of zinc can also inhibit bacterial cell growth. However, the underlying mechanism has not been fully understood. Here, we report that zinc overload in Escherichia coli cells inhibits iron-sulfur cluster biogenesis by targeting specific iron-sulfur cluster assembly proteins. Because iron-sulfur proteins are involved in diverse physiological processes, the zinc-mediated inhibition of iron-sulfur cluster biogenesis could be largely responsible for the zinc-mediated cytotoxicity. Our finding provides new insights on how intracellular zinc overload may inhibit cellular functions in bacteria. American Society for Microbiology 2019-04-18 /pmc/articles/PMC6495748/ /pubmed/30824435 http://dx.doi.org/10.1128/AEM.01967-18 Text en Copyright © 2019 Li et al. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Environmental Microbiology
Li, Jianghui
Ren, Xiaojun
Fan, Bingqian
Huang, Zhaoyang
Wang, Wu
Zhou, Huaibin
Lou, Zhefeng
Ding, Huangen
Lyu, Jianxin
Tan, Guoqiang
Zinc Toxicity and Iron-Sulfur Cluster Biogenesis in Escherichia coli
title Zinc Toxicity and Iron-Sulfur Cluster Biogenesis in Escherichia coli
title_full Zinc Toxicity and Iron-Sulfur Cluster Biogenesis in Escherichia coli
title_fullStr Zinc Toxicity and Iron-Sulfur Cluster Biogenesis in Escherichia coli
title_full_unstemmed Zinc Toxicity and Iron-Sulfur Cluster Biogenesis in Escherichia coli
title_short Zinc Toxicity and Iron-Sulfur Cluster Biogenesis in Escherichia coli
title_sort zinc toxicity and iron-sulfur cluster biogenesis in escherichia coli
topic Environmental Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6495748/
https://www.ncbi.nlm.nih.gov/pubmed/30824435
http://dx.doi.org/10.1128/AEM.01967-18
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