Structural and functional characterization of MrpR, the master repressor of the Bacillus subtilis prophage SP & beta;

Prophages control their lifestyle to either be maintained within the host genome or enter the lytic cycle. Bacillus subtilis contains the SP & beta; prophage whose lysogenic state depends on the MrpR (YopR) protein, a key component of the lysis-lysogeny decision system. Using a historic B. subtilis strain harboring the heat-sensitive SP & beta; c2 mutant, we demonstrate that the lytic cycle of SP & beta; c2 can be induced by heat due to a single nucleotide exchange in the mrpR gene, rendering the encoded MrpR(G136E) protein temperature-sensitive. Structural characterization revealed that MrpR is a DNA-binding protein resembling the overall fold of tyrosine recombinases. MrpR has lost its recombinase function and the G136E exchange impairs its higher-order structure and DNA binding activity. Genome-wide profiling of MrpR binding revealed its association with the previously identified SPbeta repeated element (SPBRE) in the SP & beta; genome. MrpR functions as a master repressor of SP & beta; that binds to this conserved element to maintain lysogeny. The heat-inducible excision of the SP & beta; c2 mutant remains reliant on the serine recombinase SprA. A suppressor mutant analysis identified a previously unknown component of the lysis-lysogeny management system that is crucial for the induction of the lytic cycle of SP & beta;.