Outer Membrane Vesicles Containing Ompa Induce Mitochondrial Fragmentation to Promote Pathogenesis and Dissemination of <i>Acinetobacter baumannii</i>

Abstract

Acinetobacter baumannii is an extracellular Gram-negative human pathogen that causes life-threatening infections but the virulence mechanisms it employs remain poorly understood. Here we report that A. baumannii secretes outer membrane vesicles (OMVs) containing the outer membrane protein A (OmpAAb) that are targeted to host cell mitochondria thereby inducing DRP1-driven mitochondrial fragmentation, ROS production and cell death. DRP1 loss reverses these phenotypes. Using intra-nasal lung infection model in mice, we show that OmpAAb is required for bacteria-induced damage to alveolar macrophages and for bacterial dissemination from the lung to other organs. Heterologous expression of OmpAAb in E. coli transfers its virulence properties to E. coli and is sufficient to induce mitochondrial fragmentation and cell death in infected cells. We describe the mechanism by which extracellular A. baumannii utilizes OmpAAb to inflict host cell damage and promotes virulence in-vitro and in-vivo and further report the host cell factor responsible for the effect.