ESR7 – TAAs as diagnostic targets

Institute for Medical Microbiology & Infection Control, Goethe University Frankfurt (Germany)
Adhesion to host cells represents the first step in the infection process and one of the decisive features in the pathogenicity of human pathogenic bacteria. The genus Bartonella harbours a variety of trimeric autotransporter adhesins (TAAs) such as the Bartonella adhesin A (BadA) of B. henselae. TAAs mediate many of the biologically properties of Bartonella spp., e.g. adherence to endothelial cells and extracellular matrix proteins. The exact molecular binding functions of BadA need to be analysed in detail to understand whether and how ‘anti-ligands’ as a new class of antibiotics might be produced. In this project we will investigate whether bacterial TAAs (here BadA) are a valuable antigen for serodiagnosis of infections, and whether BadA-specific antibodies will inhibit bacterial adherence (matrix proteins, host cells). This will be done using the human pathogen B. henselae and a quality-certified human serum library. The binding of BadA-expressing bacteria will be inhibited using poly- and monoclonal antibodies which are thought to prevent infections. Read out will be done using various in vitro and ex vivo infection models. For BadA-peptide constructions, a secondment with our partner in Oslo (Norway) is planned. For identifying antibody-specific target sequences, a secondment with our partner in Lund (Sweden) is planned. Moreover, a secondment with bioMeriéux (Lyon, France) is scheduled to analyse inhibition of bacterial adherence. For details please see: Schmidgen et al. & Kempf, J. Bacteriol. 196, 2155-65 (2014); Kaiser et al. & Kempf, Cell. Microbiol. 14, 198-209 (2012); O’Rourke et al. & Kempf, Adv. Exp. Med. Biol. 715, 51-70 (2012); Eberhardt et al. & Kempf, Proteomics 30, 1967-1981 (2009); Wagner et al. & Kempf, Int. J. Med. Microbiol. 298, 579-90 (2008); Kaiser et al. & Kempf, Cell. Microbiol 10, 2223-34 (2008) and Riess et al. & Kempf, J. Exp. Med. 200, 1267-1278 (2004).