RONNIE BERNTSSON
Structural biology of Type 4 Secretion Systems from Gram-positive bacteria
Kempestiftelserna
Multidrug resistance in bacteria, originating from conjugative gene transfer, is an increasingly common problem in today’s world. The majority of bacteria that causes hospital infections are of gram-positive origin, but so far very little is known about their conjugation systems.
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. This will lead to a deeper insight into one of the main processes responsible for horizontal gene transfer events, including the spread of antibiotic resistance genes in bacteria. It will also pave the way for future drug discovery against this type of bacteria, which are often involved in hospital infections. The proteins involved in forming the T4SS will be studied biochemically, structurally and biophysically. Since gram-positive T4SSs are very dissimilar 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.
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, since deactivation of T4SSs would lead to attenuation of the pathogen followed by easier clearance of an infection by the host immune system.
