Analysis of Acinetobacter trimeric adhesin (Ata) in multi-drug resistant clinical ilsolates and its contribution to the pathogenic potential of A. baumannii
Pathogenic bacteria specifically adhere to cell and tissue surfaces in their hosts to initiate infection. After invasion, several virulence mechanisms support persistent infection and bacterial dissemination. Adhesion to host cells and proteins of the extracellular matrix is mediated by the interaction of bacterial adhesins with corresponding host cell ligands.
Trimeric autotransporter adhesins (TAAs) are important pathogenicity factors of Gram-negative bacteria. Recently, we identified TAAs in Acinetobacter spp. by in silico screening methods. The TAA of Acinetobacter baumannii, Acinetobacter trimeric autoransporter (Ata), is modularly constructed consisting of head, stalk and membrane anchor domains with a duplication of the head domain and neck-stalk regions of different lengths. Ata is expressed on the surface of A. baumannii, mediates adherence to matrix proteins and is necessary for pathogenicity in several in vitro and in vivo infection models.
The explanation for the successful spread of multidrug-resistant A. baumannii in hospitals is assumed, primarily, to be associated with the inability to adequately treat infections caused by these multidrug-resistant bacteria and only to a lesser degree due to an increase in virulence. However, there is clearly a lack of knowledge whether and how multidrug-resistance affects pathogenicity of A. baumannii.
Our studies (i) will help to understand to what extend Ata contributes to the pathogenicity of multidrug-resistant A. baumannii and (ii) might lead to new, innovative therapeutic concepts for these difficult to treat multi-resistant pathogens (e.g., by blocking the bacterial adhesion to the host with “antiligands”).
Prof. Dr. med Volkhard A. J. Kempf
Dr. med. Stephan Göttig
Marko Weidensdorfer (PhD student)
Research Interest: Functional characterization of the trimeric autotransporter adhesin Ata in A. baumannii upon infection of the human host
Sara Riedel-Christ (technician)
Research Interest: Investigating antibiotic resistance and pathogenicity of clinical Acinetobacter isolates