Unique Features of Alarmone Metabolism in Clostridioides difficile.

ABSTRACT: The "magic spot" alarmones (pp)pGpp, previously implicated in Clostridioides difficile antibiotic survival, are synthesized by the RelA-SpoT homolog (RSH) of C. difficile (RSH_Cd) and RelQ_Cd. These enzymes are transcriptionally activated by diverse environmental stresses. RSH_Cd has previously been reported to synthesize ppGpp, but in this study, we found that both clostridial enzymes exclusively synthesize pGpp. While direct synthesis of pGpp from a GMP substrate, and (p)ppGpp hydrolysis into pGpp by NUDIX hydrolases, have previously been reported, there is no precedent for a bacterium synthesizing pGpp exclusively. Hydrolysis of the 5' phosphate or pyrophosphate from GDP or GTP substrates is necessary for activity by the clostridial enzymes, neither of whic

SUBMITTER: Poudel A 

PROVIDER: S-EPMC9017329 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature