Projekt C2 - Bartonella adhesins as diagnostic and therapeutic targets
Prof. Dr. med. Volkhard A. J. Kempf
Goethe University Frankfurt/Main
Department of Medical Microbiology
and Hospital Hygiene
University Hospital Frankfurt
Tel.: +49 69 6301 5019
Fax: +49 69 6301 83431
- Project description
Background: In the Andes of South America, Bartonella bacilliformis causes severe infections of humans with a mortality of up to 90% („Oroya-fever”). Pathological angiogenic skin lesions are a further sign of infections („verruga peruana“). The pathogen is transmitted via sand flies (Lutzomyia verrucarum), the cellular niches are erythrocytes and endothelial cells.1 B. henselae which is the most frequent Bartonella species in Europe, expresses a vasculoproliferative surface protein (Bartonella adhesin A, BadA) which belongs to the class of „trimeric autotransporter-adhesins“ (TAAs). BadA is immunodominant suggesting that it might be a suitible candidate protein for diagnostics and vaccine development2-4 In B. bacilliformis, BadA homologous proteins (Brps) have been identified.1 It is likely, that Brp plays a crucial role in the infection biology of B. bacilliformis; however, further pathogenicity factors and immunodominant proteins have also been identified.5 Research with B. bacilliformis is difficult: beside technical challenges (fastidious and slow growing, genetics) only very few human isolates and no human sera (decisive to identify, e.g., immundominant proteins) are available.
Scientific goals: Immundominant proteins of B. bacilliformis will be analysed for diagnostic and vaccination strategies: (i) molecular characterisation of immunogenic proteins (e.g., BrpA), (ii) establishing of an antibody-based sero-diagnostic approach for B. bacilliformis infections, (iii) inhibition of the BrpA-mediated bacteria-endothelial interactions (therapeutic and vaccination aspects).
Literatur C4: 1. Kaiser et al. (2011) Int J Med Microbiol 3011:7-15 2. Riess et al. (2004) J Exp Med 200:1267-78 3. O’Rourke et al. (2012) Adv Exp Med Biol 715:51-70 4. O’Rourke et al. (2015) Cell Microbiol 17:1447-63 5. Henriquez-Camacho et al. (2015) Int J Peptides doi: 10.1155/2015/702784