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鲍曼不动杆菌外膜孔蛋白Omp33 - 36是一种毒力因子,可诱导人类细胞凋亡并调节自噬。

The Acinetobacter baumannii Omp33-36 porin is a virulence factor that induces apoptosis and modulates autophagy in human cells.

作者信息

Rumbo Carlos, Tomás María, Fernández Moreira Esteban, Soares Nelson Cruz, Carvajal Micaela, Santillana Elena, Beceiro Alejandro, Romero Antonio, Bou Germán

机构信息

Department of Microbiology, Complejo Hospitalario Universitario A Coruña-INIBIC, La Coruña, Spain.

Department of Microbiology, Complejo Hospitalario Universitario A Coruña-INIBIC, La Coruña, Spain

出版信息

Infect Immun. 2014 Nov;82(11):4666-80. doi: 10.1128/IAI.02034-14. Epub 2014 Aug 25.

Abstract

Acinetobacter baumannii is an extracellular opportunistic human pathogen that is becoming increasingly problematic in hospitals. In the present study, we demonstrate that the A. baumannii Omp 33- to 36-kDa protein (Omp33-36) is a porin that acts as a channel for the passage of water. The protein is found on the cell surface and is released along with other porins in the outer membrane vesicles (OMVs). In immune and connective cell tissue, this protein induced apoptosis by activation of caspases and modulation of autophagy, with the consequent accumulation of p62/SQSTM1 (sequestosome 1) and LC3B-II (confirmed by use of autophagy inhibitors). Blockage of autophagy enables the bacterium to persist intracellularly (inside autophagosomes), with the subsequent development of cytotoxicity. Finally, we used macrophages and a mouse model of systemic infection to confirm that Omp33-36 is a virulence factor in A. baumannii. Overall, the study findings show that Omp33-36 plays an important role in the pathogenesis of A. baumannii infections.

摘要

鲍曼不动杆菌是一种细胞外机会性人类病原体,在医院中引发的问题日益严重。在本研究中,我们证明鲍曼不动杆菌的33至36 kDa外膜蛋白(Omp33-36)是一种孔蛋白,可作为水通过的通道。该蛋白存在于细胞表面,并与外膜囊泡(OMV)中的其他孔蛋白一起释放。在免疫和结缔细胞组织中,这种蛋白通过激活半胱天冬酶和调节自噬诱导细胞凋亡,从而导致p62/SQSTM1(sequestosome 1)和LC3B-II的积累(通过使用自噬抑制剂得以证实)。自噬的阻断使细菌能够在细胞内(自噬体内)持续存在,随后产生细胞毒性。最后,我们使用巨噬细胞和全身感染小鼠模型证实Omp33-36是鲍曼不动杆菌的一种毒力因子。总体而言,研究结果表明Omp33-36在鲍曼不动杆菌感染的发病机制中起重要作用。

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