Exploring modulation of host cell signaling mediated by secreted bacterial factors.
We aim to clarify mechanisms and pathways modulated by bacteria in host cells through release of protein, e.g. toxins, associated with membrane vesicles. This includes recent findings about modulation of epigenetic regulation and cell senescence in normal host cells and cancer cells. We will explore our new knowledge for development of potential therapeutic interventions in cancer and inflammatory diseases.
Pathogenicity of bacteria is dependent on several secretion systems to export virulence factors into the environment or into the target host cells. These secreted or injected factors result in interference with or stimulation of host cellular processes. Recently, the contribution of bacterial membrane vesicles (MVs) has been recognised as a means of secretion occurring among several bacterial pathogens. In our studies of V. cholerae - host interactions, the type VI secretion system (T6SS) and the MV-mediated secretion have emerged as particularly relevant.
MVs, are spherical particles that typically range between 25 – 200 nm in diameter and are constantly being discharged from the bacteria during growth. Our earlier discoveries show that MVs can play a role of physiological relevance in toxin release from bacteria. We demonstrated that MVs are effective long distance vehicles of multifunctional cargos, from DNA and RNA to proteins including several toxins and immune modulators. It is anticipated that further detailed understanding of the mechanisms and roles of these secretion systems may open for future novel targets and strategies in development of new antimicrobials and anti-cancer drugs.