Sensing the Reducing Power to Determine the Cell Fate: Flavin Redox-Switches in Signal Transduction.

Balancing electron donors and acceptors is crucial for bacterial cell to control both anabolism and catabolism rates and to keep at minimum ROS production and the resulting oxidative stress. Efficiency of nutrients uptake and assimilation is therefore linked to the availability of electron acceptors, to finally re-cycle reduced intracellular electron shuttles belonging to catabolism via respiratory chain. In case of excess reduced electron shuttles (named high reducing power), partially reduced respiratory complexes can be populated, which in turn produce ROS and oxidative stress. This is particularly relevant in the biofilm structure, where the stratified community copes with variable environment characterized by nutrients and oxygen gradients; shortage of electron acceptors found in the deeper layers of bacterial biofilm potentially favors the intracellular increase in reducing power. To avoid this risk, bacterial biofilm promotes extracellular electron flux and re-shapes biofilm morphology to increase the surface in contact with oxygen (i.e., electron acceptors). Sensing the reducing power is therefore a strategy to re-adapt the cellular metabolism to the variation of the environmental conditions, to promote the production of defense systems scavenging ROS and finally to tune bacterial behavior, such as chemotaxis and biofilm morphology. In this review, the role of the flavins in sensing the reducing power via signal transducers is discussed, with a focus on selected examples deeply characterized so far. The possible interference of such sensing activity as a strategy to treat infections and biofilm by means of electroceutical tools, is also discussed as future perspective.