The Virulence-Associated Protein A (VapA) of Rhodococcus equi as a central manipulator of infected macrophages

• Applicant: Professor Dr. Albert Haas
• Subject Area: Medical Microbiology and Mycology, Hygiene, Molecular Infection Biology
• Term: since 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 420695171

Rhodococcus equi is an important intracellular macrophage-localized pathogen in immunosuppressed humans and in foals. Using a mouse-based model, we have shown that VapA, as a central virulence factor of R. equi, changes intracellular transport in macrophages and increases the permeability of phagosome and lysosome membranes for protons. VapA action leads to the accumultation of lipid vesicles within the pathogen-containing phagosome. Here we plan to study the contribution of VapA-induced vesicle formation into the R. equi-containing vacuole (‘microautophagy’) to R. equi nutrition and pathogenesis. We will further study the regulation of vapA by environmental factors. Altogether these studies will contribute to understand how a single virulence factor (VapA) can govern all virulence events identified to date and how VapA helps supply the pathogen with nutrients. This knowledge will benefit not only research into bacterial pathogenicity in general but will also help design proper therapeutic targets and measures.

• DFG Programme: Research Grants