Toxin-antitoxin systems homologous with relBE of Escherichia coli plasmid P307 are ubiquitous in prokaryotes

Toxin-antitoxin systems encoded by bacterial plasmids and chromosomes speci fy two proteins, a cytotoxin and an antitoxin. The antitoxins neutralize th e cognate toxins by forming tight complexes with them. The antitoxins are u nstable due to degradation by cellular proteases (Lon or Clp), whereas the toxins are stable. Here we show that orf7 (denoted relB(P307)) and orf6 (de noted relE(P307)) of Escherichia coli plasmid P307 are homologous to the re lBE genes of E. coli and constitute a two-component toxin-antitoxin system: (i) relE(P307) encodes a cytotoxin lethal or inhibitory to host cells; (ii ) relB(P307) encodes an antitoxin that prevents the lethal action of the re lE-encoded toxin; (iii) RelB(P307) antitoxin is degraded by Lon protease; ( iv) RelB(P307) antitoxin autoregulates the relBE operon of P307 at the leve l of transcription; (v) RelE(P307) toxin acts as a co-repressor of transcri ption; and (vi) the relBE system stabilizes a mini-P307 replicon by the kil ling of plasmid-free cells. Using database searching, we found relBE homolo gues on the chromosomes of many Gram-negative and Grampositive bacteria. Ev en more surprising, numerous relBE-homologous gene systems are present on t he chromosomes of Archae. Thus, toxin-antitoxin systems homologous with rel BE of E. coli are ubiquitous in prokaryotic organisms. (C) 1999 Academic Pr ess.