Xenophagy of invasive bacteria is differentially activated and modulated via a TLR-TRAF6-Beclin1 axis in echinoderms.
Xenophagy of invasive bacteria is differentially activated and modulated via a TLR-TRAF6-Beclin1 axis in echinoderms.
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DOI：
10.1016/j.jbc.2022.101667
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发表时间：
2022-03
期刊：
影响因子：
--
通讯作者：
Li C
中科院分区：
文献类型：
--
作者：
Shao Y;Wang Z;Chen K;Li D;Lv Z;Zhang C;Zhang W;Li C
在海洋环境中，生物体面临着许多微生物的挑战，虽然不同的致病细菌物种的异嗜性调节仍然相对未知。在这里，我们解决了这个问题，使用仿刺参作为模式。通过全基因组筛选，我们鉴定了39个保守的自噬相关基因，为海参自噬调控提供了分子基础。此外，在不同的自噬试验中观察到两种革兰氏阴性菌，灿烂弧菌和大肠杆菌，但不是革兰氏阳性菌，藤黄微球菌的异嗜性。令人惊讶的是，在大肠杆菌攻击组中发现比在灿烂弧菌攻击组中显著更高的自噬能力。为了证实这些发现，分离了两种不同的脂多糖，LPSV. splendidus和LPSE. coli;我们发现这些LPS种类差异性地激活体腔细胞异嗜性。为了探索介导异嗜水平差异的分子机制，我们使用siRNA敲低测定并证实LPSV. splendidus介导的异嗜依赖于AjTLR 3介导的途径，而LPSE. coli介导的异嗜依赖于AjToll。此外，不同AjTLR的激活导致AjTRAF 6泛素化和随后的AjBeclin 1的K63连接的泛素化的激活。因此，LPSV. splendidus诱导的AjTLR 3途径同时激活AjA 20的表达，这降低了AjBeclin 1的K63连接的泛素化程度并削弱了自噬的诱导;然而，这一发现在LPSE. coli中并不明显。我们目前的研究结果提供了第一个证据表明，异食可以由不同的细菌物种产生差异自噬棘皮动物水平的差异诱导。
In marine environments, organisms are confronted with numerous microbial challenges, although the differential regulation of xenophagy in response to different pathogenic bacterial species remains relatively unknown. Here, we addressed this issue using Apostichopus japonicus as a model. We identified 39 conserved autophagy-related genes by genome-wide screening, which provided a molecular basis for autophagy regulation in sea cucumbers. Furthermore, xenophagy of two Gram-negative bacteria, Vibrio splendidus and Escherichia coli, but not a Gram-positive bacteria, Micrococcus luteus, was observed in different autophagy assays. Surprisingly, a significantly higher autophagy capacity was found in the E. coli–challenged group than in the V. splendidus–challenged group. To confirm these findings, two different lipopolysaccharides, LPSV. splendidus and LPSE. coli, were isolated; we found that these LPS species differentially activated coelomocyte xenophagy. To explore the molecular mechanism mediating differential levels of xenophagy, we used an siRNA knockdown assay and confirmed that LPSV. splendidus-mediated xenophagy was dependent on an AjTLR3-mediated pathway, whereas LPSE. coli-mediated xenophagy was dependent on AjToll. Moreover, the activation of different AjTLRs resulted in AjTRAF6 ubiquitination and subsequent activation of K63-linked ubiquitination of AjBeclin1. Inversely, the LPSV. splendidus-induced AjTLR3 pathway simultaneously activated the expression of AjA20, which reduced the extent of K63-linked ubiquitination of AjBeclin1 and impaired the induction of autophagy; however, this finding was no t evident with LPSE. coli. Our present results provide the first evidence showing that xenophagy could be differentially induced by different bacterial species to yield differential autophagy levels in echinoderms.
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