Endospore cortex biogenesis
Bacterial endospores survive treatment that regularly kills cells. For example, they show extreme resistance to heat, toxic chemicals and radiation. The cortex layer of the endospore consists mainly of peptidoglycan and is essential for the heat-resistance but is not required for endospore assembly. Cell wall peptidoglycan is necessary for growth of bacteria and its synthesis is blocked by many antibiotics. Endospore cortex provides an excellent experimental system for fundamental studies on peptidoglycan synthesis and this is exploited in our research project.
Synthesis of endospore cortex depends on the transpeptidase activity of SpoVD, a spore-specific enzyme of the poorly understood high-molecular weight class B penicillin-binding proteins. The major portion of the SpoVD protein in the sporulating cell faces the intermembrane space of the forespore and has a transpeptidase domain, that binds penicillin and is essential for cortex sytnthesis, and two domains of unknown function.
Aims with the research project are to elucidate the functions of the different domains of SpoVD in peptidoglycan synthesis to gain understanding of both endospore and peptidoglycan morphogenesis at the molecular level. The research topic is of considerable medicinal interest because peptidoglycan synthesis is an effective target for several classes of antibiotics in clinical use and drugs to come. Endospores are also of large clinical concern because they are formed by major pathogens, e.g. Clostridum difficile, and very difficult to eradicate.