The role of the dynamin membrane-remodelling proteins in developmentally controlled cell division in Streptomyces

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Streptomyces are harmless soil bacteria that resemble moulds in that they are filamentous, rather than unicellular organisms. They are vital to human welfare because they are the source of the vast majority of antibiotics used by doctors to cure infectious diseases, as well as providing us with numerous other medicines used, for example, to treat cancer, and to help organ transplant patients. Streptomyces reproduce themselves by dividing specialised reproductive filaments called 'aerial hyphae' into long chains of spores, in a process called 'morphological differentiation'. Antibiotic production is tightly coordinated with morphological differentiation. Morphological differentiation to form dormant spores requires each aerial hypha to synchronously lay down 50 or more regularly spaced, specialized walls called 'sporulation septa'. These sporulation septa grow in from the sides of the aerial hyphae, with the membrane of the hyphae invaginating around the ingrowing wall, until both membrane and wall fuse in the middle. We have discovered two proteins called 'dynamins' that are required for this massive cell division event to take place normally. The dynamin proteins are involved in remodeling the membranes as they invaginate and fuse, but somehow they are also required to stabilize the molecular machinery that synthesizes the ingrowing cell wall. The aim of this grant application is to discover how the dynamins achieve these functions at the molecular level. We also know that the dynamins are present in the closely related (but experimentally very difficult) bacterium Mycobacterium tuberculosis, which causes the fatal disease tuberculosis, and that the cell division machinery we will be studying in Streptomyces is closely related to the cell division machinery in this killer bug. Thus, this work may also provide significant insights into the cell division machinery of another bacterium important to human health. Finding ways to inhibit cell division in pathogenic bacteria could lead to more effective treatments for the diseases they cause.