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  • 标题:CydDC functions as a cytoplasmic cystine reductase to sensitize Escherichia coli to oxidative stress and aminoglycosides
  • 本地全文:下载
  • 作者:Alexander Mironov ; Tatyana Seregina ; Konstantin Shatalin
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:2020
  • 卷号:117
  • 期号:38
  • 页码:23565-23570
  • DOI:10.1073/pnas.2007817117
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要:l -cysteine is the source of all bacterial sulfurous biomolecules. However, the cytoplasmic level of l -cysteine must be tightly regulated due to its propensity to reduce iron and drive damaging Fenton chemistry. It has been proposed that in Escherichia coli the component of cytochrome bd -I terminal oxidase, the CydDC complex, shuttles excessive l -cysteine from the cytoplasm to the periplasm, thereby maintaining redox homeostasis. Here, we provide evidence for an alternative function of CydDC by demonstrating that the cydD phenotype, unlike that of the bona fide l -cysteine exporter eamA , parallels that of the l -cystine importer tcyP. Chromosomal induction of eamA , but not of cydDC , from a strong pLtetO-1 promoter (P tet ) leads to the increased level of extracellular l -cysteine, whereas induction of cydDC or tcyP causes the accumulation of cytoplasmic l -cysteine. Congruently, inactivation of cydD renders cells resistant to hydrogen peroxide and to aminoglycoside antibiotics. In contrast, induction of cydDC sensitizes cells to oxidative stress and aminoglycosides, which can be suppressed by eamA overexpression. Furthermore, inactivation of the ferric uptake regulator ( fur) in P tet - cydDC or P tet - tcyP cells results in dramatic loss of survival, whereas catalase ( katG ) overexpression suppresses the hypersensitivity of both strains to H 2 O 2 . These results establish CydDC as a reducer of cytoplasmic cystine, as opposed to an l -cysteine exporter, and further elucidate a link between oxidative stress, antibiotic resistance, and sulfur metabolism.
  • 关键词:bacteria ; oxidative stress ; l -cysteine ; aminoglycosides ; cytochrome
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