Magnus stårsta
The goal of our research is to understand how contact-dependent growth inhibition CDI systems work and to identify their role in bacterial biology. Our 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.
Antibiotic resistance is an increasing problem worldwide and new means of treating infections are of essence if we wish to treat bacterial infections in the future. Another factor that complicates treatment options is that we are starting to understand how important the normal flora is for our health. The human body contains more bacterial cells than human cells and these bacteria are an important first line of defense against bacterial pathogens.
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In addition, the bacteria of the normal flora help us digest our food and have been shown to be important for diverse processes, ranging from our mood to development of disease like cancer. One example of a new way of treating infections in the future is to use bacterial probiotics to strengthen the first line of defense against incoming pathogens.
But how this defense actually works is still unknown. Recently, a new system that bacteria use to stop the growth of other bacteria was identified and called contact dependent growth inhibition CDI after its mechanism of action. To be able to stop the growth of other bacteria, the bacteria with these systems must come in direct contact with the bacteria they wish to inhibit and deliver a toxin to it.
The effects of internally expressed Contact-Dependent growth Inhibition (CDI) toxins in bacteria
In addition, the inhibition is restricted to bacteria of a certain species because the delivery of toxin requires species-specific receptors on the target cell surface. To develop more effective probiotics, we wish to arm probiotic bacteria with CDI systems that target pathogenic bacteria specifically. This would mean that already beneficial bacterial probiotic can be developed into targeted killing machines that specifically identify and stop the growth of the bacterial pathogen in question.
The goal of my research is to understand how contact-dependent growth inhibition CDI systems work and to identify their role in bacterial biology.
Koskiniemi lab
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. 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.
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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. Chromosome-level genome assembly and annotation of the social amoeba Dictyostelium firmibasis. Part of Scientific Data, Colicins and T6SS-based competition systems enhance enterotoxigenic E. Part of Gut microbes, Part of Chest, p. Part of Nucleic Acids Research, p.
All-electrical antibiotic susceptibility testing within 30 min using silicon nano transistors. Part of Sensors and actuators. B, Chemical, Escherichia coli EC93 deploys two plasmid- encoded class I contact- dependent growth inhibition systems for antagonistic bacterial interactions.