Discovery of new bacterial toxins could be key to fighting infections

Researchers have discovered a new group of bacterial toxins that can kill harmful bacteria and fungi, opening the door to potential new treatments for infections. These toxins, present in more than 100,000 microbial genomes, can destroy the cells of bacteria and fungi without harming other organisms.

The study, published in Natural microbiologydiscovered how certain bacteria use these toxins to compete with other microbes, and the results could lead to new ways to fight infections, especially as antibiotic resistance becomes a growing concern.

The work, led by Hebrew University researchers Dr. Asaf Levy of the Institute of Environmental Sciences, Dr. Neta Schlezinger of the Koret School of Veterinary Medicine and Dr. Netanel Tzarum of the Institute of life sciences, in collaboration with researchers from the Weizmann Institute of Science, Profs. . Jacob Klein and Meital Oren-Suissa, along with Professor Herbert Schmidt of the University of Hohenheim, have revealed a new arsenal of bacterial toxins that can combat human and plant infectious diseases.

These toxins, encoded in the genome of certain bacteria, exhibit potent antibacterial and antifungal properties, providing exciting new possibilities for clinical and biotechnological applications.

Microbial competition is a natural phenomenon and bacteria have developed sophisticated methods, including toxins, to eliminate their competitors. The most famous examples of natural compounds used competitively in nature are antibiotics produced by bacteria and fungi.

In this study, Dr. Levy’s team developed an innovative computational approach to identify previously unknown toxin protein domains, 100 to 150 amino acids long, in more than 105,000 microbial genomes. These protein toxins, called polymorphic toxins, play a crucial role in microbial warfare, targeting and killing competing microorganisms in different ecosystems.

The research team successfully validated nine newly discovered toxins, each representing a large evolutionarily conserved family, demonstrating their ability to cause cell death in Escherichia coli and Saccharomyces cerevisiae when expressed in these model organisms . Of particular note, five antitoxin genes, also called immunity genes, have been identified that protect toxin-producing bacteria from self-destruction.

Interestingly, the toxins exhibit potent antifungal activity against a range of pathogenic fungi, while leaving some species of invertebrates and macrophages intact. The experimental results of the study suggest that these toxins act primarily as effective enzymes targeting essential cellular processes, such as cell membrane, DNA or cell division. Structural analysis of two protein-toxin-immunity complexes further confirmed that some of these toxins possess DNase activity, which can degrade DNA in target cells.

Notably, the structure shows that the toxin is positively charged in its DNA binding site to bind negatively charged DNA, while the antitoxin protein is negatively charged to prevent the toxin from binding to target DNA .

“Our results expand our understanding of how bacteria use toxins in competition with other microbes and open exciting avenues for future research into much-needed antimicrobial agents against human and plant bacterial and fungal pathogens,” said Dr. Levy. “The potential for these toxins to serve as the basis for new clinical treatments or biotechnological innovations is particularly interesting.”

This research not only improves knowledge of microbial toxins, but also sheds light on their potential therapeutic use. The team’s discovery could pave the way for new antimicrobial strategies, especially as the world grapples with the rise of antibiotic-resistant pathogens.

The study has broad implications both for understanding microbial interactions in different environments and for the development of next-generation antimicrobials. By revealing the mechanisms by which these toxins operate, research offers hope for new treatments in the ongoing fight against bacterial and fungal infections.