Actinomycetes produce 70% of all known antibiotics, most of which are produced by members of the genus Streptomyces. Furthermore, streptomycetes produce a plethora of other medically relevant... Show moreActinomycetes produce 70% of all known antibiotics, most of which are produced by members of the genus Streptomyces. Furthermore, streptomycetes produce a plethora of other medically relevant natural products as well as industrial enzymes. Streptomyces is a multicellular mycelial organism, and has a complex life cycle involving sporulation. Cell division in Streptomyces is very different from bacteria with planktonic growth, such as the model organisms E. coli and B. subtilis. Understanding the way cell division is controlled in Streptomyces is not only important for fundamental understanding of cell division in multicellular microorganisms, but may be applied to manipulate its morphology in liquid cultures, for more efficient industrial fermentation. Several novel cell division-related proteins were studied in this research, providing new functional insights into their function during growth and development and their localization in time and space in the Streptomyces mycelium. Cell division proteins do not function alone, but are members of a complex interaction network, which work in a disciplined team. The work described in this PhD thesis shows that streptomycetes have different control systems for cell division, which are complementary to each other to ensure cell division occurs at the right place and at the right time. Show less
Streptomycetes are Gram-positive soil-dwelling bacteria, in appearance similar to filamentous fungi. The SsgA-like proteins or SALPs, of which streptomycetes typically have at least five paralogues... Show moreStreptomycetes are Gram-positive soil-dwelling bacteria, in appearance similar to filamentous fungi. The SsgA-like proteins or SALPs, of which streptomycetes typically have at least five paralogues, control specific steps of sporulation-specific cell division in streptomycetes. The expression level of SsgA, the best studied SALP, has a rather dramatic effect on septation and on hyphal morphology, which is not only of relevance for our understanding of (developmental) cell division but has also been succesfully applied in industrial fermentation, to improve growth and production of filamentous actinomycetes. The different regulation of ssgA transcription in different Streptomyces species, is at least one of the reasons why some strains are able to produce spores in liquid-grown mycelium, while others cannot. By far the most conserved SALP is SsgB, which is most likely is the archetypal SALP, with only SsgB orthologues occurring in all morphologically complex actinomycetes. SsgB is essential for sporulation of Streptomyces, and orthologues have a universally conserved function in actinomycete morphogenesis. Show less
During developmental cell division in sporulation-committed aerial hyphae of streptomycetes, up to a hundred septa are simultaneously produced, in close harmony with synchromous chromosome... Show moreDuring developmental cell division in sporulation-committed aerial hyphae of streptomycetes, up to a hundred septa are simultaneously produced, in close harmony with synchromous chromosome condensation and segregation. Several unique protein families are involved in the control of this process, including that of the SsgA-like proteins (SALPs). While SsgA and SsgB are essential for sporulation-specific cell division in S. coelicolor, SsgC-G are responsible for correct DNA segregation/condensation, spore wall synthesis, autolytic spore separation, or exact septum localisation. The SALPs are a novel protein family that acts through timing and localisation of the activity of penicillin-binding proteins and autolysins, thus controlling important steps during the initiation and the completion of sporulation. The formation of septa is initiated by the formation of a ring of the tubulin-like protein FtsZ (the Z-ring), functioning as a scaffold for the construction of septa. Subsequently, other cell division proteins are recruited to the Z-ring, forming the divisome. In S. coelicolor, the cell division proteins FtsE and FtsX participate during autolytic spore separation, and most likely function by re-importing peptidoglycan subunits for recycling. The cytoskeletal protein MreB is involved in cell shape determination and chromosome segregation in many rod-shaped bacteria. In S. coelicolor, the actin-like proteins MreB and Mbl are not essential for vegetative growth but exert their function in the formation of environmentally stable spores, thereby primarily influencing the assembly of the spore wall. Show less
