Title: An activator regulates the DNA damage response and anti-phage defense networks in Moraxellaceae

Shuang Song, Shitong Zhong, Qiucheng Shi, Xiangkuan Zheng, Yue Yao, Wenxiu Wang, Shanhou Chen, Zijun Huang, Dongyue An, Hong Xu, Bing Tian, Ye Zhao, Liangyan Wang, Wei Zhang, Xiaoting Hua, Yunsong Yu, Huizhi Lu, Lu Fan, Yuejin Hua

Abstract

DNA-damage chemicals, including many antibiotics, often induce prophage induction and phage outbreaks within microbial communities, posing a significant threat to bacterial survival. Moraxellaceae strains are clinically relevant due to their remarkable resistance to antibiotics and radiation. However, the cellular-level regulation mechanisms that underlie their DNA damage response and anti-phage defense remain extensively unexplored. Here, we report a WYL family protein, DdaA, that has replaced the ubiquitous SOS system during the evolution of Moraxellaceae. DdaA functions as an activator and directly regulates the transcriptional networks of both DNA damage response and anti-phage defense genes under conditions of DNA damage stress. Our findings elucidate a pathway that shows how these bacteria enhance their immunity under DNA damage and shed light on controlling the resistance of Moraxellaceae strains in clinical practice.

Link: https://academic.oup.com/nar/article/53/16/gkaf828/8242474