New methods to stop the spread of bacterial infections

A study led by scientists from the Zaidín Experimental Station (CSIC) has identified a superfamily of proteins that includes more than 6.300 receptors widespread among bacteria. The advance could open new strategies to combat pathogens

The search for new tools to combat pathogenic bacteria is a global priority. Bacteria need to adapt to different environments in order to survive and, therefore, they use bacterial receptors in order to adjust their physiology and ensure their survival in changing environments.

A team from the Zaidín Experimental Station (EEZ-CSIC), in collaboration with the Laboratory of Crystallographic Studies of the Andalusian Institute of Earth Sciences (IACT-CSIC) and the Ohio State University (USA), has identified a large family of bacterial receptors with common characteristics.

Specifically, they have verified that they have the ability to join the purines, a type of organic molecules, through a specific pattern conserved in bacterial proteins. These purines include degradation products of nucleic acids and plant compounds such as caffeine and theophylline.

This significant advance, published in the magazine Nature Communications., could open new avenues for the development of methods to combat bacterial infections, by interfering with these receptors.

«One strategy to combat pathogenic bacteria is to block the signals that activate their virulence, preventing them from infecting and damaging the host»

One of the strategies used to combat pathogenic bacteria consists of block signals that trigger virulence, that is, prevent bacteria from activating the mechanisms that allow them to infect and harm the host.

This process is based on intervening in the functioning of the receptors of these bacteria. However, the lack of knowledge about the signals that activate bacterial receptors makes it difficult to develop effective methods to block them, and therefore prevent virulence. 

The importance of ligands

Using a combination of structural biology, bioinformatics, protein biochemistry, and microbiology techniques, the authors of this study show that the identified superfamily includes more than 6.300 receivers which are widespread in numerous bacterial species, including those that are pathogens of humans and plants.

Likewise, these have crucial roles in the regulation of genetic activity, cellular metabolism, internal signaling and the movement capacity of bacteria.

The researchers used the bacteria Vibrio cholerae, the causative agent of cholera, as a model in their study, demonstrating that the binding of these receptors to compounds such as theophylline, a purine abundant in tea, increases levels of a second messenger that controls virulence.

«Our novel approach will allow us to predict signals in other families of domains and will have a great impact on microbiology»

Tino Krell (EEZ-CSIC)

This work thus opens a new avenue of study to combat pathogens, interfering with their ability to detect external signals. In the same way, it is possible to validate an innovative method to identify and classify large groups of bacterial proteins that bind to compounds called ligands.

Furthermore, it is demonstrated that purine derivatives are important external chemical signals that influence bacterial functions, opening new possibilities for the treatment of this type of infections.

“The approach we have used in the study is novel and will allow us to predict the signals identified by other families of domains in the future, which will have an important impact on the field of microbiology,” he indicates. Tino Krell, researcher at the EEZ-CSIC.

Reference: Elizabeth Monteagudo-Cascales, et al. "Ubiquitous purine sensor modulates diverse signal transduction pathways in bacteria." Nature Communications., 2024

Source: SINC Agency

Image: EEZ-CSIC

Source: CSIC

Rights: Creative Commons