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The Acinetobacter baumannii Omp33-36 porin is a virulence factor that induces apoptosis and modulates autophagy in
Carlos Rumbo1, María Tomás2, Esteban Fernández Moreira1
1Department of Microbiology, Complejo Hospitalario Universitario A Coruña-INIBIC, La Coruña, Spain.
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.
Insights
Acinetobacter baumannii Omp33-36, a porin protein, triggers cell death and aids bacterial survival within host cells. This outer membrane protein is a key virulence factor in A. baumannii infections.
Area of Science:
- Microbiology
- Immunology
- Cell Biology
Background:
- Acinetobacter baumannii is a significant hospital-acquired pathogen.
- Understanding its virulence factors is crucial for combating infections.
Purpose of the Study:
- To investigate the role of A. baumannii Omp33-36 protein in pathogenesis.
- To elucidate the mechanisms by which Omp33-36 contributes to virulence.
Main Methods:
- Characterization of Omp33-36 as a porin involved in water transport.
- Analysis of Omp33-36-induced apoptosis and autophagy modulation in immune cells.
- Intracellular persistence studies using autophagy inhibitors.
- Validation in a mouse model of systemic infection.
Main Results:
- Omp33-36 is a porin facilitating water passage and is released via outer membrane vesicles (OMVs).
- Omp33-36 induces apoptosis and alters autophagy, leading to p62/SQSTM1 and LC3B-II accumulation.
- Inhibition of autophagy enhances intracellular bacterial persistence and cytotoxicity.
- Omp33-36 is confirmed as a virulence factor in macrophages and a systemic infection mouse model.
Conclusions:
- Omp33-36 is a crucial virulence factor in Acinetobacter baumannii infections.
- The protein contributes to pathogenesis by inducing apoptosis, modulating autophagy, and promoting intracellular survival.
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