Effect of OmpA of Acinetobacter baumannii on apoptosis in pulmonary epithelial cells and its molecular mechanism

Background: Acinetobacter baumannii (AB) is a key pathogen in hospital-acquired infections, with rising concerns around its virulence and drug resistance. Outer membrane protein A (OmpA) plays a crucial role in AB's pathogenicity, facilitating Bacterial adhesion, biofilm formation, toxin release, and immune responses. OmpA consists of two proline-rich regions, with its N-terminus forming a β-barrel transmembrane domain, allowing AB to bind host cells and invade mitochondria and the nucleus. The N-terminus triggers a Caspase cascade leading to mitochondrial damage, while the C-terminus causes DNA degradation, resulting in Apoptosis.

Methods: This study explored OmpA's role in mitochondrial damage and Apoptosis in lung tissues using in vitro and in vivo assays such as Annexin V/PI staining, HE staining, IHC, Western blotting, and immunofluorescence.

Results: In vivo experiments confirmed that OmpA deficiency significantly alleviated inflammatory damage, alveolar structural disruption, and peribronchial inflammatory cell infiltration in SD rat lung tissue. This protection was mediated by downregulating Beclin-1, JNK1, Drp-1, and Caspase-3/9 expression while upregulating Bcl-2 expression, thereby mitigating lung tissue injury in SD rats. In vitro experiments in WTRL1 cells demonstrated consistent patterns, with both the OmpA^-/-strain and the Autophagy inhibitor Chloroquine reversing the aforementioned protein expression and Apoptosis.

Conclusion: OmpA induces mitochondrial damage and Apoptosis in lung tissue cells during AB Infection.