Repression of YdaS Toxin Is Mediated by Transcriptional Repressor RacR in the Cryptic Prophage of K-12.

Horizontal gene transfer is a major driving force behind the genomic diversity seen in prokaryotes. The cryptic prophage in K-12 carries the gene for a putative transcription factor RacR, whose deletion is lethal. We have shown that the essentiality of in K-12 is attributed to its role in transcriptionally repressing toxin gene(s) called and , which are adjacent to and coded divergently to . Transcription factors in the bacterium are rarely essential, and when they are essential, they are largely toxin-antitoxin systems. While studying transcription factors encoded in horizontally acquired regions in , we realized that the protein RacR, a putative transcription factor encoded by a gene on the prophage, is an essential protein. Here, using genetics, biochemistry, and bioinformatics, we show that its essentiality derives from its role as a transcriptional repressor of the and genes, whose products are toxic to the cell. Unlike type II toxin-antitoxin systems in which transcriptional regulation involves complexes of the toxin and antitoxin, repression by RacR is sufficient to keep transcriptionally silent.