Metal Messengers: Communication in the Bacterial World through Transition-Metal-Sensing Two-Component Systems

Bacteriasurvive in highly dynamic and complex environments due,in part, to the presence of systems that allow the rapid control ofgene expression in the presence of changing environmental stimuli.The crosstalk between intra- and extracellular bacterial environmentsis often facilitated by two-component signal transduction systemsthat are typically composed of a transmembrane histidine kinase anda cytosolic response regulator. Sensor histidine kinases and responseregulators work in tandem with their modular domains containing highlyconserved structural features to control a diverse array of genesthat respond to changing environments. Bacterial two-component systemsare widespread and play crucial roles in many important processes,such as motility, virulence, chemotaxis, and even transition metalhomeostasis. Transition metals are essential for normal prokaryoticphysiological processes, and the presence of these metal ions mayalso influence pathogenic virulence if their levels are appropriatelycontrolled. To do so, bacteria use transition-metal-sensing two-componentsystems that bind and respond to rapid fluctuations in extracytosolicconcentrations of transition metals. This perspective summarizes thestructural and metal-binding features of bacterial transition-metal-sensingtwo-component systems and places a special emphasis on understandinghow these systems are used by pathogens to establish infection inhost cells and how these systems may be targeted for future therapeuticdevelopments.