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

• DOI: 10.1128/iai.02034-14
• Publication Date: 2014-08-26T03:35:50Z
• Authors: Carlos Rumbo; María Tomás; Esteban Fernández...; Nelson Cruz Soares; Micaela Carvajal; Elena Santillana; Alejandro Beceiro; Antonio Romero; Germán Bou
• Keywords: Acinetobacter baumannii; Male; Mice, Inbred BALB C; 0303 health sciences; Protein Conformation; Virulence Factors; Macrophages; Porins; Apoptosis; DNA Fragmentation; Cell Line; 3. Good health; Mice; 03 medical and health sciences; Bacterial Proteins; Autophagy; Animals; Humans; Acinetobacter Infections

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.