CydDC functions as a cytoplasmic cystine reductase to sensitize <i>Escherichia coli</i> to oxidative stress and aminoglycosides
А. С. Миронов, Т. А. Серегина, Konstantin Shatalin, Maxim Nagornykh, Р. С. Шакулов, Evgeny Nudler
Abstract
Significance The CydDC complex is involved in the assembly of cytochrome bd -I, a terminal oxidase of the respiratory chain required for growth under low oxygen conditions. It has been suggested that CydDC shuttles excessive l -cysteine from the cytoplasm to the periplasm, thereby maintaining bacterial redox homeostasis. Here, we demonstrate that the principle function of CydDC is in maintaining the reduced state of cytoplasmic l -cysteine, as opposed to exporting l -cysteine, thereby providing an important connection between sulfur metabolism, oxidative stress, and resistance to antibiotics. In particular, we establish the critical role of cytoplasmic l -cysteine in mediating the toxicity of aminoglycosides. Thus, understanding the mechanisms that control the bacterial redox state can lead to more effective strategies to counter bacterial resistance and tolerance.