Summary
Under stressful conditions, bacterial RelA-SpoT Homologue (RSH) enzymes synthesise the alarmone (p)ppGpp, a nucleotide messenger. (p)ppGpp rewires bacterial transcription and metabolism to cope with stress, and at high concentrations inhibits the process of protein synthesis and bacterial growth to save and redirect resources until conditions improve. Single domain Small Alarmone Synthetases (SAS) are RSH family members that contain the (p)ppGpp synthesis (SYNTH) domain, but lack the hydrolysis (HD) domain, and regulatory C-terminal domains of the long RSHs such as Rel, RelA and SpoT. We have discovered that multiple SAS subfamilies can be encoded in broadly distributed bicistronic operon architectures in bacteria and bacteriophages that are reminiscent of those typically seen in toxin-antitoxin (TA) operons. We have validated five of these SASs as being toxic (toxSASs), and shown that the toxicity can be neutralised by five distinct neighbouring antitoxin genes that act at the protein level.
