Dr Karrera Djoko karrera.djoko@durham.ac.uk
Associate Professor
Dr Karrera Djoko karrera.djoko@durham.ac.uk
Associate Professor
Minh-Duy Phan
Kate M. Peters
Mark J. Walker
Mark A. Schembri
Alastair G. McEwan
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.
Djoko, K. Y., Phan, M., Peters, K. M., Walker, M. J., Schembri, M. A., & McEwan, A. G. (2017). Interplay between tolerance mechanisms to copper and acid stress in Escherichia coli. Proceedings of the National Academy of Sciences, 114(26), 6818-6823. https://doi.org/10.1073/pnas.1620232114
Journal Article Type | Article |
---|---|
Acceptance Date | May 23, 2017 |
Online Publication Date | Jun 13, 2017 |
Publication Date | Jun 13, 2017 |
Deposit Date | Sep 6, 2017 |
Publicly Available Date | Oct 13, 2017 |
Journal | Proceedings of the National Academy of Sciences |
Print ISSN | 0027-8424 |
Electronic ISSN | 1091-6490 |
Publisher | National Academy of Sciences |
Peer Reviewed | Peer Reviewed |
Volume | 114 |
Issue | 26 |
Pages | 6818-6823 |
DOI | https://doi.org/10.1073/pnas.1620232114 |
Accepted Journal Article
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Perspectives on Metals in Microbiology
(2022)
Journal Article
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