Repression of YdaS Toxin Is Mediated by Transcriptional Repressor RacR in the Cryptic <i>rac</i> Prophage of Escherichia coli K-12

Abstract

Horizontal gene transfer is a major driving force behind the genomic diversity seen in prokaryotes. The cryptic <i>rac</i> prophage in <i>Escherichia coli</i> K-12 carries the gene for a putative transcription factor RacR, whose deletion is lethal. We have shown that the essentiality of <i>racR</i> in <i>E. coli</i> K-12 is attributed to its role in transcriptionally repressing toxin gene(s) called <i>ydaS</i> and <i>ydaT</i>, which are adjacent to and coded divergently to <i>racR</i>. <b>IMPORTANCE</b> Transcription factors in the bacterium <i>E. coli</i> are rarely essential, and when they are essential, they are largely toxin-antitoxin systems. While studying transcription factors encoded in horizontally acquired regions in <i>E. coli</i>, we realized that the protein RacR, a putative transcription factor encoded by a gene on the <i>rac</i> 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 <i>ydaS</i> and <i>ydaT</i> 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 <i>ydaS</i> transcriptionally silent.