Abstract
Guanosine penta- or tetraphosphate (known as (p)ppGpp) serves as second messenger to respond to nutrient downshift and other environmental stresses, a phenomenon called stringent response. Accumulation of (p)ppGpp promotes the coordinated inhibition of macromolecule synthesis, as well as the activation of stress response pathways to cope and adapt to harmful conditions. In Escherichia coli, the (p)ppGpp level is tightly regulated by two enzymes, the (p)ppGpp synthetase RelA and the bifunctional synthetase/hydrolase SpoT. We recently identified the small protein YtfK as a key regulator of SpoT-mediated activation of stringent response in E. coli. Here, we further characterized the regulation of ytfK. We observed that ytfK is subjected to catabolite repression and is positively regulated by the cyclic AMP (cAMP)-cAMP receptor protein (CRP) complex. Importantly, YtfK contributes to SpoT-dependent accumulation of (p)ppGpp and cell survival in response to glucose starvation. Therefore, regulation of ytfK by the cAMP-CRP appears important to adjust (p)ppGpp level and coordinate cellular metabolism in response to glucose availability.
Highlights
Bacteria have evolved efficient stress response mechanisms to quickly adjust cell growth and metabolism according to challenging environments
Given that cyclic AMP (cAMP)-cAMP receptor protein (CRP) complex plays an important role in carbon sources catabolism and positively regulates the ytfK expression, we naturally investigated the role of YtfK in SpoT-dependent (p)ppGpp accumulation under glucose starvation
In E. coli, two homologous enzymes work in concert to control (p)ppGpp level: the (p)ppGpp synthetase RelA and the bifunctional synthetase/hydrolase SpoT
Summary
Bacteria have evolved efficient stress response mechanisms to quickly adjust cell growth and metabolism according to challenging environments. The hyperphosphorylated derivatives of GDP and GTP, guanosine tetra- and pentaphosphate (collectively named (p)ppGpp), are the central signaling molecules of the stringent response (Cashel and Gallant, 1969; Potrykus and Cashel, 2008). These alarmones allow rapid and robust stress adaptation by affecting gene expression and metabolism (Cashel, 1969; Potrykus and Cashel, 2008; Hauryliuk et al, 2015; Liu et al, 2015; Steinchen and Bange, 2016). The tight balance between both reciprocal activities constitutes a crucial point of regulation for fine tuning
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