文献类型：期刊文献

英文题名：Type III secretion system effector YfiD inhibits the activation of host poly(ADP-ribose) polymerase-1 to promote bacterial infection

作者：Zhou, Mengqing[1];Liu, Yabo[1];Zhang, Yibei[1,2,3];Ma, Yue[1,2,3];Zhang, Yuanxing[2,3,4];Choi, Sang Ho[5];Shao, Shuai[1,2,3];Wang, Qiyao[1,2,3,4,6]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai, Peoples R China;[2]Shanghai Engn Res Ctr Maricultured Anim Vaccines, Shanghai, Peoples R China;[3]Lab Aquat Anim Dis MOA, Shanghai, Peoples R China;[4]Qingdao Natl Lab Marine Sci & Technol, Lab Marine Fisheries Sci & Food Prod Proc, Qingdao, Peoples R China;[5]Seoul Natl Univ, Dept Agr Biotechnol, Natl Res Lab Mol Microbiol & Toxicol, Seoul, South Korea;[6]Shanghai Haosi Marine Biotechnol Co Ltd, Shanghai, Peoples R China

年份：2024

卷号：7

期号：1

外文期刊名：COMMUNICATIONS BIOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001158054600001)】；

基金：This work was supported by grants from the National Natural Science Foundation of China (32373183, 32130108), the National Key Research and Development Program (2022YFE0101200), the Shanghai Municipal Science and Technology Commission Technical Leader Project (21XD1431900), and the China Agriculture Research System of MOF and MARA (CARS-47).

语种：英文

摘要：Modulation of cell death is a powerful strategy employed by pathogenic bacteria to evade host immune clearance and occupy profitable replication niches during infection. Intracellular pathogens employ the type III secretion system (T3SS) to deliver effectors, which interfere with regulated cell death pathways to evade immune defenses. Here, we reveal that poly(ADP-ribose) polymerase-1 (PARP1)-dependent cell death restrains Edwardsiella piscicida's proliferation in mouse monocyte macrophages J774A.1, of which PARP1 activation results in the accumulation of poly(ADP-ribose) (PAR) and enhanced inflammatory response. Moreover, E. piscicida, an important intracellular pathogen, leverages a T3SS effector YfiD to impair PARP1's activity and inhibit PAR accumulation. Once translocated into the host nucleus, YfiD binds to the ADP-ribosyl transferase (ART) domain of PARP1 to suppress its PARylation ability as the pharmacological inhibitor of PARP1 behaves. Furthermore, the interaction between YfiD and ART mainly relies on the complete unfolding of the helical domain, which releases the inhibitory effect on ART. In addition, YfiD impairs the inflammatory response and cell death in macrophages and promotes in vivo colonization and virulence of E. piscicida. Collectively, our results establish the functional mechanism of YfiD as a potential PARP1 inhibitor and provide more insights into host defense against bacterial infection. The bacterial T3SS effector YfiD interacts with the catalytic domain of host PARP1 during infection. Inhibition of PARP1 activity impairs the pro-inflammatory response against bacterial infection.