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

Toxin-antitoxin systems encoded by bacterial plasmids and chromosomes specify two proteins, a cytotoxin and an antitoxin. The antitoxins neutralize the cognate toxins by forming tight complexes with them. The antitoxins are unstable due to degradation by cellular proteases (Lon or Clp), whereas the toxins are stable. Here we show that orf7 (denoted relBP307) and orf6 (denoted relEP307) of Escherichia coli plasmid P307 are homologous to the relBE genes of E. coli and constitute a two-component toxin-antitoxin system: (i) relEP307 encodes a cytotoxin lethal or inhibitory to host cells; (ii) relBP307 encodes an antitoxin that prevents the lethal action of the relE-encoded toxin; (iii) RelBP307 antitoxin is degraded by Lon protease; (iv) RelBP307 antitoxin autoregulates the relBE operon of P307 at the level of transcription; (v) RelEP307 toxin acts as a co-repressor of transcription; and (vi) the relBE system stabilizes a mini-P307 replicon by the killing of plasmid-free cells. Using database searching, we found relBE homologues on the chromosomes of many Gram-negative and Gram-positive bacteria. Even more surprising, numerous relBE-homologous gene systems are present on the chromosomes of Archae. Thus, toxin-antitoxin systems homologous with relBE of E. coli are ubiquitous in prokaryotic organisms. Copyright 1999 Academic Press.