Interplay between tolerance mechanisms to copper and acid stress in Escherichia coli

Djoko, Karrera Y., Phan, Minh-Duy, Peters, Kate M., Walker, Mark J. , Schembri, Mark A. and McEwan, Alastair G. (2017) Interplay between tolerance mechanisms to copper and acid stress in Escherichia coli. Proceedings of the National Academy of Sciences of the United States of America, 114 26: 6818-6823. doi:10.1073/pnas.1620232114


Author Djoko, Karrera Y.
Phan, Minh-Duy
Peters, Kate M.
Walker, Mark J.
Schembri, Mark A.
McEwan, Alastair G.
Title Interplay between tolerance mechanisms to copper and acid stress in Escherichia coli
Formatted title
Interplay between tolerance mechanisms to copper and acid stress in Escherichia coli
Journal name Proceedings of the National Academy of Sciences of the United States of America   Check publisher's open access policy
ISSN 1091-6490
0027-8424
Publication date 2017-06-13
Sub-type Article (original research)
DOI 10.1073/pnas.1620232114
Open Access Status Not yet assessed
Volume 114
Issue 26
Start page 6818
End page 6823
Total pages 6
Place of publication Washington, DC, United States
Publisher National Academy of Sciences
Language eng
Abstract Copper (Cu) is a key antibacterial component of the host innate immune system and almost all bacterial species possess systems that defend against the toxic effects of excess Cu. The Cu tolerance system in Gram-negative bacteria is composed minimally of a Cu sensor (CueR) and a Cu export pump (CopA). The cueR and copA genes are encoded on the chromosome typically as a divergent but contiguous operon. In Escherichia coli, cueR and copA are separated by two additional genes, ybaS and ybaT, which confer glutamine (Gln)-dependent acid tolerance and contribute to the glutamate (Glu)-dependent acid resistance system in this organism. Here we show that Cu strongly inhibits growth of a ∆copA mutant strain in acidic cultures. We further demonstrate that Cu stress impairs the pathway for Glu biosynthesis via glutamate synthase, leading to decreased intracellular levels of Glu. Addition of exogenous Glu rescues the ∆copA mutant from Cu stress in acidic conditions. Gln is also protective but this relies on the activities of YbaS and YbaT. Notably, expression of both enzymes is up-regulated during Cu stress. These results demonstrate a link between Cu stress, acid stress, and Glu/Gln metabolism, establish a role for YbaS and YbaT in Cu tolerance, and suggest that subtle changes in core metabolic pathways may contribute to overcoming host-imposed copper toxicity.
Formatted abstract
Copper (Cu) is a key antibacterial component of the host innate immune system and almost all bacterial species possess systems that defend against the toxic effects of excess Cu. The Cu tolerance system in Gram-negative bacteria is composed minimally of a Cu sensor (CueR) and a Cu export pump (CopA). The cueR and copA genes are encoded on the chromosome typically as a divergent but contiguous operon. In Escherichia coli, cueR and copA are separated by two additional genes, ybaS and ybaT, which confer glutamine (Gln)-dependent acid tolerance and contribute to the glutamate (Glu)-dependent acid resistance system in this organism. Here we show that Cu strongly inhibits growth of a ∆copA mutant strain in acidic cultures. We further demonstrate that Cu stress impairs the pathway for Glu biosynthesis via glutamate synthase, leading to decreased intracellular levels of Glu. Addition of exogenous Glu rescues the ∆copA mutant from Cu stress in acidic conditions. Gln is also protective but this relies on the activities of YbaS and YbaT. Notably, expression of both enzymes is up-regulated during Cu stress. These results demonstrate a link between Cu stress, acid stress, and Glu/Gln metabolism, establish a role for YbaS and YbaT in Cu tolerance, and suggest that subtle changes in core metabolic pathways may contribute to overcoming host-imposed copper toxicity.
Keyword GOGAT
Acid tolerance
Copper stress
Glutamate biosynthesis
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
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School of Chemistry and Molecular Biosciences
 
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Created: Fri, 16 Jun 2017, 13:59:04 EST by Mrs Louise Nimwegen on behalf of School of Chemistry & Molecular Biosciences