TPR domain assigns versatility of BcTir/Tpr system against viral infection

Abstract

SummaryNAD+-derived signal produced by TIR domain triggered the host immune responses. The ubiquitous TPR domain involved in signal recognition and effector activation were found widely assembled with the TIR domain. However, the immune roles of these assemblies remain elusive. Here, a two-gene operon, one containing a TIR domain, designated as BcTir, and the other, BcTpr, fromBacillus cereus, exhibited anti-phage immunity. BcTpr, but not BcTir, exhibited NADase activity to produce the cyclic ADPR (cADPR) isomer and mediate NAD+depletion. Noticeably, the truncated N terminus of BcTpr only depleted NAD+unless at the presence of TPR domain to generate cADPR isomer unveiling its role played for glycosite selection. In addition, the BcTir/Tpr system significantly repressed viral proliferation and increased oxidation resistance by scavenging excessive reactive oxygen species (ROS) upon phage infection. These findings unraveled a multifunctional role of the BcTir/Tpr system during immune responses.In BriefThe bacterial BcTir/Tpr system was identified with the ability to protect against phage infection via NAD+depletion, viral replication repression, and ROS homeostasis, in which BcTpr played a dual role in NAD+-derived signal production and NAD+depletion.HighlightsThe BcTir/Tpr system works as a BcTir-BcTpr complex against phage infection.BcTpr, instead of BcTir, generates the NAD+-derived cADPR isomer through its glycosidase domain at N terminus.The amount of cADPR isomer production is regulated by the helix numbers of the TPR domain at C terminus of BcTpr.The BcTir/Tpr system can depress phage proliferation and decrease ROS production upon phage infection.