The molecular and physiological mechanisms involved in the transition of microbial cells from a resting state to the active
vegetative state are critically relevant for solving problems in fields ranging from microbial ecology to
infection microbiology. Cyanobacteria that cannot fix
nitrogen are able to survive prolonged periods of
nitrogen starvation as chlorotic cells in a dormant state. When provided with a usable
nitrogen source, these cells re-green within 48 hr and return to vegetative growth. Here we investigated the
resuscitation of chlorotic Synechocystis sp. PCC 6803 cells at the physiological and molecular levels with the aim of understanding the awakening process of a dormant bacterium. Almost immediately upon
nitrate addition, the cells initiated a highly organized
resuscitation program. In the first phase, they suppressed any residual photosynthetic activity and activated respiration to gain energy from
glycogen catabolism. Concomitantly, they restored the entire translational apparatus,
ATP synthesis, and
nitrate assimilation. After only 12-16 hr, the cells re-activated the synthesis of the photosynthetic apparatus and prepared for metabolic re-wiring toward photosynthesis. When the cells reached full photosynthetic capacity after ∼48 hr, they resumed cell division and entered the vegetative cell cycle. An analysis of the transcriptional dynamics during the
resuscitation process revealed a perfect match to the observed physiological processes, and it suggested that non-coding RNAs play a major regulatory role during the lifestyle switch in awakening cells. This genetically encoded program ensures rapid colonization of habitats in which
nitrogen starvation imposes a recurring growth limitation.