TY  - JOUR
A1  - Tiku, Varnesh
A1  - Kofoed, Eric M.
A1  - Yan, Donghong
A1  - Kang, Jing
A1  - Xu, Min
A1  - Reichelt, Mike
A1  - Đikić, Ivan
A1  - Tan, Man-Wah
T1  - Outer membrane vesicles containing OmpA induce mitochondrial fragmentation to promote pathogenesis of Acinetobacter baumannii
T2  - Scientific reports
N2  - Acinetobacter baumannii is a highly antibiotic resistant Gram-negative bacterium that causes life-threatening infections in humans with a very high mortality rate. A. baumannii is an extracellular pathogen with poorly understood virulence mechanisms. Here we report that A. baumannii employs the release of outer membrane vesicles (OMVs) containing the outer membrane protein A (OmpAAb) to promote bacterial pathogenesis and dissemination. OMVs containing OmpAAb are taken up by mammalian cells where they activate the host GTPase dynamin-related protein 1 (DRP1). OmpAAb mediated activation of DRP1 enhances its accumulation on mitochondria that causes mitochondrial fragmentation, elevation in reactive oxygen species (ROS) production and cell death. Loss of DRP1 rescues these phenotypes. Our data show that OmpAAb is sufficient to induce mitochondrial fragmentation and cytotoxicity since its expression in E. coli transfers its pathogenic properties to E. coli. A. baumannii infection in mice also induces mitochondrial damage in alveolar macrophages in an OmpAAb dependent manner. We finally show that OmpAAb is also required for systemic dissemination in the mouse lung infection model. In this study we uncover the mechanism of OmpAAb as a virulence factor in A. baumannii infections and further establish the host cell factor required for its pathogenic effects.
KW  - Microbiology
KW  - Pathogens
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/62734
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-627340
SN  - 2045-2322
N1  - The authors thank Genentech Inc. for generously funding the study.
VL  - 11
IS  - art. 618
SP  - 1
EP  - 16
PB  - Macmillan Publishers Limited, part of Springer Nature
CY  - [London]
ER  -