ABOUT

We focus on host-pathogen interactions and investigate cell biology processes and signaling pathways involved in pathogen-induced host cytoskeleton remodeling.
We use several human bacterial pathogens and purified toxins to uncover the mechanisms underlying 1) bacterial usurpation of host cytoskeleton function and 2) host resistance and survival to infection.

RESEARCH

While the pathogen exploits cellular functions to hide from immune defense and establish within the host, the host deploys resistance mechanisms to repair damage and survive to infection. We have been studying the Listeria monocytogenes infectious process and the host responses to intoxication by bacterial pore-forming toxins.
In particular, we assessed host cytoskeleton alterations induced during intracellular infection by Listeria monocytogenes and upon intoxication with purified pore-forming toxins, which are major virulence factors of human bacterial pathogens. We have found that during infection of epithelial cells, L. monocytogenes exploits the function of actomyosin, keratins and tubulin to promote cellular invasion and cell-to-cell spread. In addition, we showed that upon plasma membrane damage induced by pore-forming toxins, human epithelial cells undergo massive actomyosin remodeling. The assembly of cortical actomyosin structures in the target cell appears to be critical to plasma membrane repair, recovery of cell integrity and host survival to infection.

Collaborations

• J. Leong, Tufts University, Boston-USA
• A. Lacy-Hulbert, Benaroya Research Institute, Seattle-USA
• S. Mostowy, Imperial College, London-UK
• J. Sellers, NIH-NHLBI, Bethesda-USA
• D. Cabanes, IBMC/i3S, Porto-Portugal
• A. X. Carvalho, IBMC/i3S, Porto-Portugal

Grants

• POCI-01-0145-FEDER-030863 - Enlighten host plasma membrane repair mechanisms upon bacterial pore-forming toxins attack
• NORTE-01-0145-FEDER-000012 – Structured Program on Bioengineered Therapies for Infectious Diseases and Tissue Regeneration