Activation and modulation of the host response to DNA damage by an integrative and conjugative element

Mobile genetic elements help drive horizontal gene transfer and bacterial evolution. Conjugative elements and temperate bacteriophages can be stably maintained in host cells. They can alter host physiology and regulatory responses and typically carry genes that are beneficial to their hosts. We found that ICE<i>Bs1</i>, an integrative and conjugative element (ICE) of <i>Bacillus subtilis</i>, inhibits the host response to DNA damage (the SOS response). Activation of ICE<i>Bs1</i> before DNA damage reduced host cell lysis that was caused by SOS-mediated activation of two resident prophages. Further, activation of ICE<i>Bs1</i> itself activated the SOS response in a subpopulation of cells, and this activation was attenuated by the functions of the ICE<i>Bs1</i> genes <i>ydcT</i> and <i>yddA</i> (now <i>ramT</i> and <i>ramA</i>; <i>ram</i> for RecA modulator). Double-mutant analyses indicated that RamA functions to inhibit and RamT functions to both inhibit and activate the SOS response. Both RamT and RamA caused a reduction in RecA filaments, one of the early steps in activation of the SOS response. We suspect that there are several different mechanisms by which mobile genetic elements that generate single-stranded DNA (ssDNA) during their life cycle inhibit the host SOS response and RecA function, as RamT and RamA differ from the known SOS inhibitors encoded by conjugative elements.IMPORTANCEBacterial genomes typically contain mobile genetic elements, including bacteriophages (viruses) and integrative and conjugative elements, that affect host physiology. ICEs can excise from the chromosome and undergo rolling-circle replication, producing ssDNA, a signal that indicates DNA damage and activates the host SOS response. We found that following excision and replication, ICE<i>Bs1</i> of <i>B. subtilis</i> stimulates the host SOS response and that ICE<i>Bs1</i> encodes two proteins that limit the extent of this response. These proteins also reduce the amount of cell killing caused by resident prophages following their activation by DNA damage. These proteins are different from those previously characterized that inhibit the host SOS response and represent a new way in which ICEs can affect their host cells.