ESR6 – Analysis of TAA-dependent bacterial adhesion to matrix and host cells

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 biological 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 ‘antiligands’ as a new class of antibiotics might be produced. In this project we will investigate how bacterial pathogens bind to their respective binding partners (matrix proteins, host cells). This will be done using the human pathogen B. henselae and BadA-mutants. The binding of BadA-expressing bacteria to matrix proteins (e.g. fibronectin) and host cells will be analysed. Peptides will be modelled and produced which shall inhibit bacterial adhesion to matrix and host cell surfaces. Read out will be done using various in vitro and ex vivo infection models. For mutant construction and peptide synthesis, a secondment with our partner in Leeds (UK) is planned. To analyse bacterial binding mechanisms (NMR), a secondment with our partner in Oslo (Norway) is planned. Moreover, a secondment with Biomode (Portugal) is scheduled to analyse bacterial adherence. For details please see: O’Rourke et al. & Kempf, Cell. Microbiol. 17, 1447-63 (2015); 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); Müller et al. & Kempf, Infect. Immun. 79, 2544-2553 (2011); Kaiser et al. & Kempf, Cell. Microbiol 10, 2223-34 (2008); and Riess et al. & Kempf, J. Exp. Med. 200, 1267-1278 (2004).