Linking glucose metabolism to the stringent response through the PTS

pppGpp and ppGpp (here abbreviated as ppGpp) are signaling molecules synthesized throughout the bacterial domain of life, serving as second messengers that respond to nutritional deprivation, a phenomenon called the stringent response. ppGpp accumulation causes the coordinated inhibition of macromolecule synthesis resulting in growth arrest, as well as the activation of a number of stress responses to alleviate problems resulting from the nutritional deprivation. In Escherichia coli , there are two enzymes responsible for synthesizing ppGpp: RelA and SpoT. However, SpoT’s primary activity is ppGpp hydrolysis to prevent uncontrolled ppGpp production, which is lethal. In PNAS, Lee et al. (1) report a link between SpoT activity and the function of the phosphoenolpyruvate-dependent sugar transferase system (PTS), thereby connecting sugar metabolism with the stringent response. Surprisingly, the connection between these two major cellular pathways is conferred by regulator of SigmaD (Rsd), a well-characterized antisigma factor. Rsd binds to the cell’s major sigma factor, σ70, reducing its interaction with core RNA polymerase (RNAP) (2⇓⇓–5). Thus, Rsd facilitates transcription from promoters recognized by alternative RNAP holoenzymes instead of promoters recognized by the major RNAP holoenzyme, Eσ70. However, Lee et al. (1) show that Rsd’s regulatory role in ppGpp metabolism is unlinked to its role as an antisigma. In most proteobacterial species like E. coli , ppGpp binds directly to two sites on RNAP, increasing or decreasing transcription initiation depending on the kinetic … [↵][1]1To whom correspondence should be addressed. Email: rgourse{at}bact.wisc.edu. [1]: #xref-corresp-1-1