The Global Influence of Sodium on Cyanobacteria in Resuscitation from Nitrogen Starvation

SIMPLE SUMMARY: Dormancy and resuscitation are key processes to bacterial survival. In the absence of combined nitrogen sources, the non-diazotrophic model cyanobacterium Synechocystis sp. PCC 6803 turns into a metabolically quiescent state during a process termed chlorosis, enabling long-term survival. When nitrogen sources reappear, the cells resuscitate in a process that follows a highly orchestrated program. Here, we describe the essential role of sodium in the resuscitation process. We show that in addition to its role in the bioenergetics of chlorotic cells, sodium is involved in nitrogen compound assimilation, pH regulation, and the synthesis of key metabolites. ABSTRACT: Dormancy and resuscitation are key to bacterial survival under fluctuating environmental conditions. In the absence of combined nitrogen sources, the non-diazotrophic model cyanobacterium Synechocystis sp. PCC 6803 enters into a metabolically quiescent state during a process termed chlorosis. This state enables the cells to survive until nitrogen sources reappear, whereupon the cells resuscitate in a process that follows a highly orchestrated program. This coincides with a metabolic switch into a heterotrophic-like mode where glycogen catabolism provides the cells with reductant and carbon skeletons for the anabolic reactions that serve to re-establish a photosynthetically active cell. Here we show that the entire resuscitation process requires the presence of sodium, a ubiquitous cation that has a broad impact on bacterial physiology. The requirement for sodium in resuscitating cells persists even at elevated CO(2) levels, a condition that, by contrast, relieves the requirement for sodium ions in vegetative cells. Using a multi-pronged approach, including the first metabolome analysis of Synechocystis cells resuscitating from chlorosis, we reveal the involvement of sodium at multiple levels. Not only does sodium play a role in the bioenergetics of chlorotic cells, as previously shown, but it is also involved in nitrogen compound assimilation, pH regulation, and synthesis of key metabolites.