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

Abstract

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 OmpAstrain 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.