Explore the molecular details of conjugation via Type 4 Secretion Systems in Gram-positive bacteria

The goal of this project is to determine the molecular structure and function of conjugation complexes belonging to Type IV Secretion Systems (T4SSs) from Gram-positive bacteria, which are so far mainly uncharted.

This will lead to a deeper insight into one of the main processes responsible for horizontal gene transfer events, through which antibiotic resistance genes and other virulence factors spread in between bacteria.

It will also pave the way for future drug discovery against this type of bacteria, which are often involved in hospital acquired infections.The proteins involved in forming the T4SS will be studied biochemically, structurally and biophysically. While some T4SSs of Gram-negative bacteria are fairly well understood, Gram-positive T4SSs are not.

Since Gram-positive T4SSs are highly divergent from their Gram-negative counterparts, little can be deduced from the few Gram-negative systems so far studied. Furthermore, they occur in a number of pathogens, such as enterococci, streptococci and staphylococci.

Another aspect that makes Gram-positive T4SSs interesting is that they are used to efficiently transfer not only antibiotic resistance, but also virulence factors.

This makes them attractive targets for the development of novel anti-virulence drugs; deactivation of T4SSs would lead to attenuation of the pathogen followed by easier clearance of an infection by the host immune system.