Molecular mechanisms of bacteria-host interactions

The main purpose is to clarify how bacterial secreted factors influence host cell signalling pathways. In general, virulence factors are required for pathogenicity to occur regardless of the host.

We discovered a new fitness factor, the MakABE tripartite protein toxin in V. cholerae using C. elegans as a predatory non-vertebrate host model.

MakA alone can also operate as an effector inducing autophagy and apoptosis in mammalian cells, and we discovered that it forms tube-like superstructures with lipids at low pH, revealing a novel mechanism for a bacterial toxin.We also elucidate roles of bacterial membrane vesicles (BMVs) in host interactions and bacterial pathogenicity, as well as in potential medical and biotechnological applications.

Their usage in precision medicine approaches against infections and non-infectious illnesses, like cancer, will rely on increased knowledge and understanding of their roles for both microbiome and the host.Specific aims:1) Mechanisms of pore formation by MakABE toxin2) How MakA toxicity in C. elegans is pH dependent3) MakA´s impact in C. elegans and human cells on PIP5K1A-mediated signalling4) MakA´s influence on immune cell signalling5) MakA´s potential targets in mammalian cells6) The effects of phospholipase on host cell signalling7) Epigenetic effects of non-pathogenic E. coli BMVs on host cells8) The role of the commensal E. coli protein ClyA in host interactions9) The therapeutic potential of BMV-based precision medicine