A fundamental question in biology that remains to be understood is how cell shapes are genetically encoded and enzymatically generated. Spheres and rods are among the most common shapes adopted by walled bacteria. The bacterial cell wall, formed by peptidoglycan, largely determines cell shape. When bacteria reproduce by binary fission (division), the shapes of the two daughter cells are already determined by their mother cell. For this reason, it is difficult to explore the origin of cell shape using healthy bacterial cells. Taking advantage of a sphere-to-rod morphological transition during the germination of the bacterium Myxococcus xanthus, we propose to explore the mechanisms underlying the generation and maintenance of rod-like cell shapes. Cells of M. xanthus change back and forth between rods and spheres at different life stages. Rod- shaped vegetative cells thoroughly degrade their walls and shrink into uniformly sized spherical cells that then mature into spores. Unlike endospore formation in Bacillus species, whole M. xanthus cells convert to spores. As the spores of M. xanthus germinate, cells rebuild their walls and reestablish rod shape without preexisting templates. This unique morphological transition provides a rare opportunity to visualize de novo cell wall synthesis (CWS) and bacterial morphogenesis. To understand the mechanism of morphogenesis in M. xanthus, we propose three specific aims. First, to reveal the mechanism of de novo CWS during germination, we will test the hypothesis that a defined pattern of cell wall growth is required for the establishment of rod shape. Second, to elucidate the mechanism by which the MreB cytoskeleton supports rod shape during germination, we will test the hypothesis that MreB determines rod shape by guiding the motion of the CWS machinery. Third, to reveal the mechanism by which cell polarity regulates CWS and rod shape in germinating spores, we will test the hypothesis that the establishment of cell polarity is necessary for the sphere-to-rod transition. Because the peptidoglycan cell wall is widely conserved among bacteria, we expect that our results with M. xanthus will reveal fundamental mechanisms of morphogenesis, which is difficult to study in other bacteria.
The overall objective of this project is to answer a fundamental question in biology: how bacteria generate their defined cell shapes. Taking advantage of the natural sphere-to-rod morphological transition of the bacterium Myxococcus xanthus during germination, we propose to reveal the mechanisms by which bacteria establish rod-like cell shapes. Because the cell wall, which determines cell shape, is essential for the survival of many bacterial pathogens, understanding its mechanism may uncover new approaches to combat bacterial infection.
