FIG 4.

Major events during development of Streptomyces. Nutrient stress is a major trigger of development, leading to the accumulation of ppGpp, resulting in cessation of early growth and repression of the nutrient sensory DasR protein by cell wall-derived metabolites following PCD of the substrate mycelium. Bld proteins and environmental signals control the procession toward aerial growth and antibiotic production. The developmental master regulator BldD (when bound to tetrameric cyclic-di-GMP) represses the transcription of genes for many key developmental regulatory proteins, including WhiB, WhiG, SsgA, and SsgB, as well as FtsZ. Chaplins and SapB provide a supportive hydrophobic layer to allow aerial hyphae to become erect and break through the moist soil surface. White proteins control aerial growth, whereby WhiAB and SsgB likely play a role in growth cessation. Eventually, FtsZ accumulates and localizes to septum sites in an SsgAB-dependent manner. Ladders of FtsZ are formed, which subsequently delimit the spore compartments. Chromosome condensation and segregation are followed by septum closure and spore maturation. The onset of antibiotic production typically correlates temporally to the transition from vegetative to aerial growth. Solid black arrows represent major transitions in development. Dark dotted lines indicate transcriptional control (arrows for activation, ovals for repression).