Contact-dependent growth inhibition in bacteria and the use of armed probiotics in the prevention and/or treatment of infections

The goal of my research is to understand how contact-dependent growth inhibition (CDI) systems work and to identify their role in bacterial biology. My vision is that through increased understanding of cell-to-cell interactions between bacteria we can learn more about bacterial biology, ecology and pathology as well as employ these systems in changing bacterial behavior and propagation. I believe that in the future, probiotic bacteria armed with CDI systems could be used in the prevention and/or treatment of bacterial infections like, gastroenteritis, inflammatory bowel diseases and infections of the urinary tract.

Contact-dependent growth inhibition is a recently discovered phenomenon where bacteria inhibit the growth of other bacteria in a contact-dependent manner. CDI can be mediated through a few different pathways. The first discovered CDI system consists of a two-partner secretion system where the CdiB protein transports the large CdiA protein to the cell surface. CdiA has a highly divergent C-terminal end that contains the toxin domain and is delivered to target cells through a yet uncharacterized mechanism. To protect inhibition from self, a small CdiI protein binds specifically to its cognate toxin and prevents inhibition.

The second, more recently discovered CDI pathway consists of Rhs-proteins that were recently shown to mediate CDI in both gram-negative and gram-positive bacteria. Although first discovered in the Enterobacteriacae, rhs is common throughout β-, γ- and δ-proteobacteria and genes encoding distantly related YD-peptide repeat proteins are found in Gram-positive bacteria and in higher vertebrates. Similarly to the first discovered CDI system, Rhs proteins contain a highly variable C-terminal toxin domain that are delivered to target cells and are accompanied by small highly specific immunity proteins that protect cells from self-inhibition.

The first discovered CDI system has some very unique traits, for example the inhibition observed seems to be strictly species specific and will only target cells expressing the right type of receptor. Recent evidence indicates that the system can even discriminate between subspecies of E.coli, which make CDI systems highly interesting as potential targeted antimicrobials.