Two signaling molecules control the growth and behavior of bacteria

Bacteria are considered to be true experts in survival. Their rapid adaptive response to changing environmental conditions is based, among other things, on two competing signaling molecules. As the “Yin and Yang” of metabolic control, they decide the lifestyle of the bacteria, as reported by researchers from the University of Basel. The new findings also play a role in the context of bacterial infections.

Whether they are pathogens, deep-sea microbes or soil-dwelling organisms, in order to survive, microorganisms must be able to quickly adapt to various changes in their environment, including nutrient depletion. Bacteria owe their extraordinary ability to quickly adapt to adverse living conditions to small signaling molecules.

Scientists led by Professor Urs Jenal and Professor Tilman Schirmer of Biozentrum, University of Basel, have now discovered that bacteria use two chemically related signaling molecules to adapt their lifestyle to prevailing living conditions. The researchers present their findings in the latest issue of Nature Microbiology. Like Yin and Yang, the two molecules embody two forces that mutually control bacterial growth and metabolism.

Bacterium with two different lifestyles

Researchers investigated the antagonistic nature of the two signaling molecules ppGpp and c-di-GMP in the cell using Caulobacter crescentus as a model organism. This bacterium can take on two different roles: it can be found in a free-swimming form that is unable to divide and in a reproductive state attached to the surface.

Both lifestyle and environmental conditions are reflected in the concentration of the two signaling molecules. This information is detected by a protein that binds both signaling molecules and acts as a molecular switch, controlling the growth, metabolism and lifestyle of the bacterium.

Signaling molecules determine the lifestyle of bacteria

The ppGpp and c-di-GMP signaling molecules compete for binding with the master switch. “In swarms of bacteria with high ppGpp levels, the protein is activated, it is active,” explains Urs Jenal. “In this state, glucose consumption is in full swing. At the same time, the resulting harmful oxygen radicals are efficiently neutralized.” This ensures that the metabolic reactions adapt to the high energy needs of the mobile swimmer cells and that cell damage is avoided.

Under favorable living conditions, providing sufficient nutrients, the level of c-di-GMP constantly increases, forcing the swimmer to develop into a sessile form. “In this case, c-di-GMP displaces ppGpp from the binding pocket of the protein, changes its structure, and shuts down,” Jenal says. “This redirects metabolic reactions allowing bacteria to establish, grow and reproduce. The production of building blocks for the cell is enhanced along with adhesives for surface attack.”

Important role also in pathogens

With the molecular master switch, scientists have discovered the link between two large regulatory networks, which until now were thought to function independently. Although Caulobacter is a harmless environmental bacterium, the newly discovered “Yin and Yang” mechanism could also play an important role in pathogens.

This can prove to be of paramount importance: both ppGpp and c-di-GMP affect virulence and bacterial persistence, as well as antibiotic resistance in different ways, thus influencing the course of many infections.