McKeithen-Mead Saria, Anderson Mary E, García-Heredia Alam, Grossman Alan D
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139 USA.
bioRxiv. 2024 Oct 9:2024.10.09.617469. doi: 10.1101/2024.10.09.617469.
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, an integrative and conjugative element of , inhibits the host response to DNA damage (the SOS response). Activation of ICE before DNA damage reduced host cell lysis that was caused by SOS-mediated activation of two resident prophages. Further, activation of ICE itself activated the SOS response in a subpopulation of cells, and this activation was attenuated by the functions of the ICE genes and (now and , 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 ssDNA during their lifecycle inhibit the host SOS response and RecA function, as RamT and RamA differ from the known SOS inhibitors encoded by conjugative elements.
可移动遗传元件有助于推动水平基因转移和细菌进化。接合元件和温和噬菌体可在宿主细胞中稳定维持。它们可改变宿主生理和调节反应,通常携带对宿主有益的基因。我们发现,整合性接合元件ICE抑制宿主对DNA损伤的反应(SOS反应)。在DNA损伤之前激活ICE可减少由SOS介导的两个驻留原噬菌体激活所导致的宿主细胞裂解。此外,ICE自身的激活在一部分细胞中激活了SOS反应,并且这种激活被ICE基因ramA和ramT(现为recA modulator)的功能所减弱。双突变分析表明,RamA起到抑制作用,而RamT既起到抑制作用又起到激活SOS反应的作用。RamT和RamA都导致RecA丝状体减少,这是SOS反应激活的早期步骤之一。我们怀疑,在其生命周期中产生单链DNA的可移动遗传元件抑制宿主SOS反应和RecA功能存在几种不同机制,因为RamT和RamA不同于由接合元件编码的已知SOS抑制剂。