Bartonella quintana Type IV secretion effector BepE induced selective autophagy by conjugation with K63 poly ‐ubiquitin chain

AbstractBartonellaeffectorproteins (named Beps) are substrates of VirB type IV secretion system for translocation into host cells evolved inBartonella spp. Among these, BepE has been shown to protect cells from fragmentation effects triggered by other Beps and to promotein vivo dissemination of bacteria from the dermal site of inoculation to the bloodstream. Bacterial pathogens secreted effectors to modulate the interplay with host autophagy, either to combat autophagy to escape its bactericidal effect, or to exploit autophagy to benefit intracellular replication. Here we reported a distinct phenotype that selective autophagy in host cells is activated as a countermeasure, to attack BepE via conjugation with K63 poly ‐ubiquitin chain on BepE. We found that ectopic expression ofBartonella quintana BepE specifically induced punctate structures that co ‐localized with an autophagy marker (LC3‐II) in host cells, in addition to filopodia and membrane ruffle formation. Two tandemly arrangedBartonellaIntracellularDelivery (BID) domains in the BepE C ‐terminus, where ubiquitination of sister pairs of lysine residues were confirmed, were essential to activate host cell autophagy. Multiple poly‐ubiquitin chain linkages of K27, K29, K33 and K63 were found to be conjugated at sites of K222 and K365 on BepE, of which K63 polyubiquitination on Bep E K365 determined the selective autophagy (p62/SQSTM1 positive autophagy) independent of the PI3K pathway. Co‐localization of BepE w...

Source: Cellular Microbiology - November 21, 2018 Category: Microbiology Authors: Chunyan Wang, Jiaqi Fu, Meng Wang, Yuhao Cai, Xiuguo Hua, Yuming Du, Zhibiao Yang, Yan Li, Zhenxia Wang, Huiming Sheng, Na Yin, Xiaoyun Liu, Jane E. Koehler, Congli Yuan Tags: RESEARCH ARTICLE Source Type: research