4.4 Article

The Acinetobacter baumannii Omp33-36 Porin Is a Virulence Factor That Induces Apoptosis and Modulates Autophagy in Human Cells

期刊

INFECTION AND IMMUNITY
卷 82, 期 11, 页码 4666-4680

出版社

AMER SOC MICROBIOLOGY
DOI: 10.1128/IAI.02034-14

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资金

  1. Instituto de Salud Carlos III
  2. Miguel Servet Programme CHU A Coruna
  3. Instituto de Salud Carlos III (SERGAS/Ministerio de Sanidad)
  4. Fundacion Seneca (Comunidad Autonoma de la Region de Murcia)
  5. Magic Bullet - European Union's Directorate General for Research and Innovation, through the Seventh Framework Program for Research and Development [278232]
  6. Spanish Network for Research in Infectious Diseases [REIPI-RD12/0015]
  7. Spanish Ministry of Health/FEDER [ISCIII-FIS PI12/00552, FIS PI10/00056, PI13/02390]

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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.

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