Mycobacterium tuberculosis suppresses host DNA repair to boost its intracellular survival

• DOI: 10.1016/j.chom.2023.09.010
• Publication Date: 2023-10-16T14:26:31Z
• Authors: Shanshan Liu; Liru Guan; Cheng Peng; Yuanna Cheng; Hongyu Cheng; Fei Wang; Mingtong Ma; Ruijuan Zheng; Zhe Ji; Pengfei Cui; Yefei Ren; Liru Li; Chenyue Shi; Jie Wang; Xiaochen Huang; Xia Cai; Di Qu; Haiping Zhang; Zhiyong Mao; Haipeng Liu; Peng Wang; Wei Sha; Hua Yang; Lin Wang; Baoxue Ge
• Keywords: Macrophages; Interferon Type I; Mycobacterium tuberculosis; Interferon-beta; Urease; Nucleotidyltransferases; 3. Good health

Mycobacterium tuberculosis (Mtb) triggers distinct changes in macrophages, resulting the formation of lipid droplets that serve as a nutrient source. We discover Mtb promotes by inhibiting DNA repair responses, activation type-I IFN pathway and scavenger receptor-A1 (SR-A1)-mediated droplet formation. Bacterial urease C (UreC, Rv1850) inhibits host interacting with RuvB-like protein 2 (RUVBL2) impeding RUVBL1-RUVBL2-RAD51 complex. The suppression this increases abundance micronuclei trigger cyclic GMP-AMP synthase (cGAS)/stimulator interferon genes (STING) subsequent interferon-β (IFN-β) production. UreC-mediated IFN-β upregulates expression SR-A1 to form facilitate replication. UreC inhibition via inhibitor impaired growth within macrophages vivo. Thus, our findings identify mechanisms which cascade cellular events establish nutrient-rich replicative niche.