Abstract：
Aspects of how Burkholderia escape the host\'s intrinsic immune response to replicate in the cell cytosol remain enigmatic. Here, we show that Burkholderia has evolved two mechanisms to block the activity of Ring finger protein 213 (RNF213)-mediated non-canonical ubiquitylation of bacterial lipopolysaccharide (LPS), thereby preventing the initiation of antibacterial autophagy. First, Burkholderia\'s polysaccharide capsule blocks RNF213 association with bacteria and second, the Burkholderia deubiquitylase (DUB), TssM, directly reverses the activity of RNF213 through a previously unrecognized esterase activity. Structural analysis provides insight into the molecular basis of TssM esterase activity, allowing it to be uncoupled from its isopeptidase function. Furthermore, a putative TssM homolog also displays esterase activity and removes ubiquitin from LPS, establishing this as a virulence mechanism. Of note, we also find that additional immune-evasion mechanisms exist, revealing that overcoming this arm of the host\'s immune response is critical to the pathogen.
摘要：
伯克霍尔德菌如何逃避宿主的内在免疫反应以在细胞胞质溶胶中复制仍然是一个谜。这里,我们表明，伯克霍尔德菌已经进化出两种机制来阻断环指蛋白213（RNF213）介导的细菌脂多糖（LPS）的非规范泛素化的活性，从而防止抗菌自噬的启动。首先,伯克霍尔德菌多糖胶囊阻断RNF213与细菌的结合，其次，伯克霍尔德氏菌去泛素酶（DUB），TssM,通过先前未识别的酯酶活性直接逆转RNF213的活性。结构分析提供了对TssM酯酶活性的分子基础的见解，允许它从其异肽酶功能中分离出来。此外，假定的TSSM同系物还显示酯酶活性并从LPS中去除泛素，将其建立为毒力机制。值得注意的是，我们还发现存在额外的免疫逃避机制，揭示克服宿主免疫反应的这一臂对病原体至关重要。
