Bacteria-Derived Protein Aggregates Contribute to the Disruption of Host Proteostasis.
Bacteria-Derived Protein Aggregates Contribute to the Disruption of Host Proteostasis.
复制标题
DOI：
10.3390/ijms23094807
复制
发表时间：
2022-04-27
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
神经退行性蛋白质构象疾病的特征是宿主基因组编码的亚稳态蛋白质的错误折叠和聚集。宿主也是细菌、真菌和病毒所携带的外源基因组中编码的数千种蛋白质的家园。然而，它们对宿主蛋白质折叠稳态或蛋白质稳态的贡献仍然难以捉摸。最近的研究，包括我们之前的工作，表明细菌产物有助于内源性宿主蛋白的毒性聚集。我们将这些产品称为细菌衍生蛋白聚集体（bdpa）。此外，抗生素最近与神经退行性疾病的风险增加有关，包括帕金森病和肌萎缩侧索硬化症——可能是由于改变了人类肠道微生物群的组成。其他研究表明，疾病进展与抗生素使用之间存在负相关，支持它们对神经退行性疾病的保护作用。这些相互矛盾的研究强调了人类肠道微生物群、肠脑轴和抗生素作用的复杂性。在这里，我们使用秀丽隐杆线虫模型进一步了解细菌对宿主蛋白质折叠的影响。我们采用遗传和化学方法来证明细菌对宿主蛋白质折叠的蛋白质毒性作用与bdpa的存在有关。此外，bdpa的丰度和蛋白质毒性受到庆大霉素（一种诱导蛋白质错误折叠的氨基糖苷类抗生素）和丁酸（一种我们之前发现的影响宿主蛋白质聚集和相关毒性的短链脂肪酸）的影响。总的来说，这些结果增加了我们对蛋白质构象疾病背景下宿主-细菌相互作用的理解。
Neurodegenerative protein conformational diseases are characterized by the misfolding and aggregation of metastable proteins encoded within the host genome. The host is also home to thousands of proteins encoded within exogenous genomes harbored by bacteria, fungi, and viruses. Yet, their contributions to host protein-folding homeostasis, or proteostasis, remain elusive. Recent studies, including our previous work, suggest that bacterial products contribute to the toxic aggregation of endogenous host proteins. We refer to these products as bacteria-derived protein aggregates (BDPAs). Furthermore, antibiotics were recently associated with an increased risk for neurodegenerative diseases, including Parkinson’s disease and amyotrophic lateral sclerosis—possibly by virtue of altering the composition of the human gut microbiota. Other studies have shown a negative correlation between disease progression and antibiotic administration, supporting their protective effect against neurodegenerative diseases. These contradicting studies emphasize the complexity of the human gut microbiota, the gut–brain axis, and the effect of antibiotics. Here, we further our understanding of bacteria’s effect on host protein folding using the model Caenorhabditis elegans. We employed genetic and chemical methods to demonstrate that the proteotoxic effect of bacteria on host protein folding correlates with the presence of BDPAs. Furthermore, the abundance and proteotoxicity of BDPAs are influenced by gentamicin, an aminoglycoside antibiotic that induces protein misfolding, and by butyrate, a short-chain fatty acid that we previously found to affect host protein aggregation and the associated toxicity. Collectively, these results increase our understanding of host–bacteria interactions in the context of protein conformational diseases.
登录
查看更多内容
影响因子：
4.1
作者：
Christensen, Line Friis Bakmann;Jensen, Kirstine Friis;Otzen, Daniel Erik
通讯作者：
Otzen, Daniel Erik
影响因子：
24.5
作者：
Camilleri, Michael
通讯作者：
Camilleri, Michael
影响因子：
4.8
作者：
Balczon, Ron;Morrow, K. Adam;Stevens, Troy
通讯作者：
Stevens, Troy
影响因子：
15.1
作者：
Aho VTE;Houser MC;Pereira PAB;Chang J;Rudi K;Paulin L;Hertzberg V;Auvinen P;Tansey MG;Scheperjans F
通讯作者：
Scheperjans F
影响因子：
5
作者：
Bollen C;Dewachter L;Michiels J
通讯作者：
Michiels J