Drug Discovery 2021 After the Storm: Re-connect, Re-invent, Re-imagine

Functional analysis of Bartonella pathogenicity factors might contribute to novel therapeutic concepts

Thu19  Dec12:00pm(30 mins)
Where:
Room 3A
Prof Volkhard Kempf

Abstract

The genus Bartonella comprises a group of human pathogenic bacteria and infections can result in diverse clinical entities. While Bartonella henselae causes often a benign lymphadenopathy (“cat scratch disease”) in immunocompetent patients, the pathogen can induce vasculoproliferative tumours under immunosuppression (“bacillary angiomatosis”). Infections with Bartonella bacilliformis (endemic to South American Andes) result in a haemolytic fever (“Oroya fever”) with a case-fatality up to ~90%, followed by a chronic infection resulting also in angiogenic skin lesions (“verruga peruana”). Both B. henselae and B. bacilliformis exhibit an endothelial cell tropism and adhesion to host cells seems to be the critical event in the infection process. Bartonella spp. express “trimeric autotransporter adhesins (TAAs)”, whose molecular binding mechanisms to endothelial cells (via fibronectin bridging) have recently been resolved. Infections with B. bacilliformis lead to haemolysis due to infection of human erythrocytes, and bacterial porins and enzymes seem to play an essential role in these processes. Overcoming these pathogenicity mechanisms (adhesion to matrix proteins and host cells, haemolysis) requires a cell-specific understanding of the infection process. As some of these pathogenicity factors (TAAs) are conserved and are also expressed in multidrug-resistant pathogens (e.g., Acintobacter baumannii), anti-adhesion and in a more general way anti-virulence therapies might represent an attractive alternative to classical antibiotic treatment of bacterial infections.
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