Supervisor: vanemteadur Niilo Kaldalu (Tartu Ülikool)
Opponent: Prof. Remy Loris, PhD
Department of Biotechnology
Vrije Universiteit Brussel
Department of Structural Biology, VIB
Many bacteria attach to surfaces and enclose into slime. This type of growth is called biofilm and it provides better protection for bacteria to fight against harmful factors such as antibiotics and immune system. It has been proposed that most chronic infections are caused by bacteria growing in biofilms, which is a serious medical problem. Biofilm is enriched with temporarily non-dividing bacteria that have no specific antibiotic resistance mechanisms. These bacteria are not killed by the drug due to their dormant state. After the treatment, these cells wake up and start growing again. In these dormant cells, the toxin-antitoxin (TA) system genes are highly expressed. Toxin is a protein that inhibits some important process inside the bacterium. Many toxins cleave mRNA, thus, inhibiting protein synthesis and bacterial growth. Antitoxin is a protein that, by binding to the toxin, allows a cell to grow again. Therefore, activated toxins may result in formation of dormant cells in biofilms. The aim of the current dissertation was to examine the cross-activation between TA systems and to test whether mqsR and mqsA genes encode a new TA system in Eschericha coli. Firstly, we demonstrated that MqsR arrests cell growth and MqsA neutralizes the toxic effect of MqsR. In addition, MqsA regulates expression of the both genes, which is a characteristic for the antitoxins. Hence, we characterized and validated a new MqsRA TA system. Secondly, we proved cross-activation between different TA systems. The results indicate that TA cross-activation may be influenced by TA mRNA cleavage, through which bacteria produce more toxin compared to its antitoxin. In conclusion, this study provides new knowledge about simultaneous expression of TA systems and supports their possible role in dormancy.