Affiliation:
1. School of Biological Sciences, The University of Hong Kong, Hong Kong SAR
2. Department of Chemistry, The University of Hong Kong, Hong Kong SAR
Abstract
ABSTRACT
Adaptation to changing environments is essential to bacterial physiology. Here we report a unique role of the copper homeostasis system in adapting
Escherichia coli
to its host-relevant environment of anaerobiosis coupled with amino acid limitation. We found that expression of the copper/silver efflux pump CusCFBA was significantly upregulated during anaerobic amino acid limitation in
E. coli
without the supplement of exogenous copper. Inductively coupled plasma mass spectrometry analysis of the total intracellular copper content combined with transcriptional assay of the P
cusC
-
lacZ
reporter in the presence of specific Cu(I) chelators indicated that anaerobic amino acid limitation led to the accumulation of free Cu(I) in the periplasmic space of
E. coli
, resulting in Cu(I) toxicity. Cells lacking
cusCFBA
and another copper transporter,
copA
, under this condition displayed growth defects and reduced ATP production during fumarate respiration. Ectopic expression of the Fe-S cluster enzyme fumarate reductase (Frd), or supplementation with amino acids whose biosynthesis involves Fe-S cluster enzymes, rescued the poor growth of Δ
cusC
cells. Yet, Cu(I) treatment did not impair the Frd activity
in vitro
. Further studies revealed that the alternative Fe-S cluster biogenesis system Suf was induced during the anaerobic amino acid limitation, and Δ
cusC
enhanced this upregulation, indicating the impairment of the Fe-S cluster assembly machinery and the increased Fe-S cluster demands under this condition. Taken together, we conclude that the copper efflux system CusCFBA is induced during anaerobic amino acid limitation to protect Fe-S cluster enzymes and biogenesis from the endogenously originated Cu(I) toxicity, thus facilitating the physiological adaptation of
E. coli
.
Publisher
American Society for Microbiology
Subject
Molecular Biology,Microbiology
Cited by
89 articles.
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