Genetic analysis of the loop between helix H1 and sheet S2 of the cell division protein FtsZ in Streptomyces venezuelae

Popular science summary: How do bacteria divide? Cell division is an absolute requirement for proliferation of all bacteria and results in the bacterium being split into two by a septum. FtsZ is a protein that plays a key role in bacterial cell division. In this project, one part of the FtsZ protein was investigated with genetic methods to understand how it affects the division process. Previous results suggest that this part of FtsZ may affect a central but still poorly understood feature of the protein. Mutations in this region can lead to miss-shaped cell division, with twisted septa spiraling along the bacterial cell instead of dividing it into two daughter cells. Since many decades, we rely heavily on antibiotics to treat bacterial infections. However, the usage of antibiotics has resulted in the bacteria being resistant to some of them. For this reason, there is currently an urgent need for new types of antibiotics. By studying the cell division of bacteria, new and better targets for antibiotics might be discovered that directly interferes with their proliferation. The FtsZ protein has an important role in cell division of bacteria. FtsZ is located inside of the bacterium where it diffuses around as small monomers. At the time of cell division, the monomers start binding each other to form long protein filaments inside the bacterial cell. The filaments are then remodelled into ring-shaped structures, called Z-rings after FtsZ, that locate at the midpoint of the cell and determine the site where cell division will take place. The Z-rings recruit and organize a number of other proteins that help to couple the ring to membrane invagination and cell wall synthesis, leading to division of the bacterium into two daughter cells. Mutating a particular part of FtsZ was recently shown to interfere with bacterial cell division. The mutation resulted in undivided cells that had twisted septa spiraling along the cell. The mutation also caused the FtsZ filaments to bind to each other, and thereby forming pairwise bundles. It was therefore suggested that the loop between H1 and S2 of FtsZ, where the mutation was introduced, is very important for proper cell division in bacteria. I was interested in systematically investigating the loop between H1 and S2 of FtsZ to better understand its function, and chose the model organism Streptomyces venezuelae for this study. I introduced ten mutations in this region of FtsZ, to see which amino acid residues in this region are important for cell division in the bacterium. I found that the amino acid residues located in and directly adjacent to S2 of FtsZ are important for proper cell division in Streptomyces venezuelae. Supervisor: Klas Flardh Master´s Degree Project, 30 credits in Microbiology 2014 Department of Biology, Lund University