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Bacteria are considered to be true experts in survival. Their rapid adaptive response to changing environmental conditions is based, among other things, on two rival signaling molecules.
As the”Yin and Yang” of metabolic control they choose the lifestyle of bacteria, according to researchers in the University of Basel. The 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 have the ability to adapt quickly to diverse changes in their environment, such as nutrient depletion. Compounds owe their extraordinary ability to rapidly adjust to adverse living conditions to small signaling molecules.
Researchers headed by Professor Urs Jenal and Professor Tilman Schirmer in the Biozentrum, University of Basel, have discovered that bacteria use two chemically related signaling molecules to adapt their lifestyle to the existing dwelling conditions.
The researchers present their results in the most recent issue of”Nature Microbiology”. Like Yin and Yang, the two molecules embody two forces that control bacterial growth and metabolism reciprocally.
Bacterium with two different lifestyles The researchers investigated the antagonistic nature of the two signaling molecules ppGpp and c-di-GMP from the mobile using Caulobacter crescentus as a model organism. This bacterium can slip into two different roles: It can be found in a free-swimming form that’s unable divide and in a surface-attached, reproductive condition.
Both the lifestyle and the ecological conditions are reflected in the concentration of both signaling molecules.
Signaling molecules determine bacterial Method of life
The signaling molecules ppGpp und c-di-GMP compete for binding to the master switch. “In swarming bacteria with high levels of ppGpp, the protein is switched on; it is active,” explains Urs Jenal. “In this state, glucose intake is in full swing. Simultaneously, the consequent harmful oxygen radicals are efficiently neutralized.” This ensures, that metabolic reactions adapt to the high energy requirement of the motile swimmer cells and cell damage is averted.
Under favorable living conditions, providing sufficient nutrients, the level of c-di-GMP increases constantly, forcing the swimmer to develop into a sessile form. “In this situation, c-di-GMP displaces ppGpp in the protein binding pocket, it alters its structure and turns itself off,” says Jenal. “This redirects metabolic reactions allowing bacteria to settle, grow and reproduce. The production of building blocks for the cell is fostered along with adhesive materials for surface attachment.”
Important role also in pathogens With the molecular master switch, the scientists have found the connection between two large regulatory networks, which until today have been thought to function independently. Although Caulobacter is a harmless environmental bacterium, the recently uncovered”Yin and Yang” mechanism may also play an essential role in pathogens.
This may prove to be of crucial importance: Both ppGpp and c-di-GMP affect bacterial virulence and persistence as well as antibiotic resistance in various ways, thus influencing the path of many infections.
University of Basel
Shyp, V., et al. (2020) Reciprocal growth control by competitive binding of nucleotide second messengers to a metabolic switch in Caulobacter crescentus. Nature Microbiolgy. doi.org/10.1038/s41564-020-00809-4.