The Acinetobactertrimeric autotransporter adhesin Ata controls key virulence traits of Acinetobacter baumannii

ABSTRACTAcinetobacter baumanniiis a Gram-negative pathogen that causes a multitude of nosocomial infections. The Acinetobactertrimeric autotransporter adhesin (Ata) belongs to the superfamily of trimeric autotransporter adhesins which are important virulence factors in many Gram-negative species. Phylogenetic profiling revealed that atais present in 78% of all sequenced A. baumanniiisolates but only in 2% of the closely related species A. calcoaceticusand A. pittii. Employing a markerless atadeletion mutant of A. baumanniiATCC 19606 we show that adhesion to and invasion into human endothelial and epithelial cells depend on Ata. Infection of primary human umbilical cord vein endothelial cells (HUVECs) with A. baumanniiled to the secretion of interleukin (IL)-6 and IL-8 in a time- and Ata-dependent manner. Furthermore, infection of HUVECs by WT A. baumanniiwas associated with higher rates of apoptosis via activation of caspases-3 and caspase-7, but not necrosis, in comparison to ∆ata. Ata deletion mutants were furthermore attenuated in their ability to kill larvae of Galleria mellonellaand to survive in larvae when injected at sublethal doses. This indicates that Ata is an important multifunctional virulence factor in A. baumanniithat mediates adhesion and invasion, induces apoptosis and contributes to pathogenicity in vivo.