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Mutually constructive roles of Ail and LPS in Yersinia pestis serum survival.
Molecular Microbiology ( IF 2.6 ) Pub Date : 2020-05-27 , DOI: 10.1111/mmi.14530
Chandan Singh 1 , Hwayoung Lee 2 , Ye Tian 1 , Sara Schesser Bartra 3 , Suzanne Hower 3 , Lynn M Fujimoto 1 , Yong Yao 1 , Sergey A Ivanov 4 , Rima Z Shaikhutdinova 4 , Andrey P Anisimov 4 , Gregory V Plano 3 , Wonpil Im 2 , Francesca M Marassi 1
Affiliation  

The outer membrane is a key virulence determinant of gram‐negative bacteria. In Yersinia pestis, the deadly agent that causes plague, the protein Ail and lipopolysaccharide (LPS)6 enhance lethality by promoting resistance to human innate immunity and antibiotics, enabling bacteria to proliferate in the human host. Their functions are highly coordinated. Here we describe how they cooperate to promote pathogenesis. Using a multidisciplinary approach, we identify mutually constructive interactions between Ail and LPS that produce an extended conformation of Ail at the membrane surface, cause thickening and rigidification of the LPS membrane, and collectively promote Y. pestis survival in human serum, antibiotic resistance, and cell envelope integrity. The results highlight the importance of the Ail–LPS assembly as an organized whole, rather than its individual components, and provide a handle for targeting Y. pestis pathogenesis.

中文翻译:

Ail 和 LPS 在鼠疫耶尔森氏菌血清存活中的相互建设性作用。

外膜是革兰氏阴性菌的关键毒力决定因素。在鼠疫耶尔森氏菌(导致鼠疫的致命病原体)中,蛋白质 A11 和脂多糖 (LPS) 6通过促进对人类先天免疫和抗生素的抵抗力来提高致死率,使细菌能够在人类宿主中增殖。它们的功能高度协调。在这里,我们描述了它们如何合作促进发病。使用多学科方法,我们确定了 Ail 和 LPS 之间的相互建设性相互作用,这些相互作用在膜表面产生了 Ail 的扩展构象,导致 LPS 膜的增厚和硬化,并共同促进了鼠疫杆菌人血清中的存活率、抗生素抗性和细胞包膜完整性。结果突出了 Ail-LPS 组装作为一个有组织的整体而不是其单个组件的重要性,并为靶向鼠疫杆菌的发病机制提供了一个手柄。
更新日期:2020-05-27
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