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A widespread toxin-antitoxin system exploiting growth control via alarmone signaling

S. Jimmy, CK. Saha, T. Kurata, C. Stavropoulos, SRA. Oliveira, A. Koh, A. Cepauskas, H. Takada, D. Rejman, T. Tenson, H. Strahl, A. Garcia-Pino, V. Hauryliuk, GC. Atkinson,

. 2020 ; 117 (19) : 10500-10510. [pub] 20200428

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc20025016

Grantová podpora
BB/S00257X/1 Biotechnology and Biological Sciences Research Council - United Kingdom

E-zdroje Online Plný text

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Open Access Digital Library od 1915-01-01

Odkazy

PubMed 32345719
DOI 10.1073/pnas.1916617117
Knihovny.cz E-zdroje

Under stressful conditions, bacterial RelA-SpoT Homolog (RSH) enzymes synthesize the alarmone (p)ppGpp, a nucleotide second 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 (SASs) 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 asked whether analysis of the genomic context of SASs can indicate possible functional roles. Indeed, multiple SAS subfamilies are encoded in widespread conserved bicistronic operon architectures that are reminiscent of those typically seen in toxin-antitoxin (TA) operons. We have validated five of these SASs as being toxic (toxSASs), with neutralization by the protein products of six neighboring antitoxin genes. The toxicity of Cellulomonas marina toxSAS FaRel is mediated by the accumulation of alarmones ppGpp and ppApp, and an associated depletion of cellular guanosine triphosphate and adenosine triphosphate pools, and is counteracted by its HD domain-containing antitoxin. Thus, the ToxSAS-antiToxSAS system with its multiple different antitoxins exemplifies how ancient nucleotide-based signaling mechanisms can be repurposed as TA modules during evolution, potentially multiple times independently.

Citace poskytuje Crossref.org

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