Antibiotic resistance is a growing concern. According to the CDC, more than 2.8 million antimicrobial-resistant infections occur each year. Now, a team of researchers has discovered a new group of bacterial toxins that can kill harmful bacteria and fungi, opening the door to potential new ways to fight infections, especially those that are resistant to antibiotics.
The findings are published in Nature Microbiology in an article titled, “Systematic Discovery of Antibacterial and Antifungal Bacterial Toxins,” and revealed how some bacteria use these toxins to compete with other microbes.
Researchers led by Hebrew University researchers Asaf Levy, PhD, from the Institute of Environmental Science, Neta Schlezinger, PhD, from the Koret School of Veterinary Medicine, and Netanel Tzarum, PhD, from the Institute of Life Sciences, in collaboration with Weizmann Institute of Science researchers Jacob Klein and Meital Oren-Suissa, and Herbert Schmidt, PhD, from the University of Hohenheim, have discovered the toxins, found in over 100,000 microbial genomes, can destroy the cells of bacteria and fungi without harming other organisms.
Microbial competition is a natural phenomenon, and bacteria have evolved sophisticated methods, including toxins, to eliminate competitors. The most famous examples of natural compounds used in competition in nature are antibiotics produced by bacteria and fungi.
In this study, Levy’s team developed a computational approach to identify previously undiscovered toxin protein domains, which are 100–150 amino acids long, within over 105,000 microbial genomes. These protein toxins, referred to as polymorphic toxins, play a critical role in microbial warfare, targeting and killing competing microorganisms in different ecosystems.
The research team validated nine newly discovered toxins, each representing a large evolutionary conserved family, demonstrating their ability to cause cell death in both Escherichia coli and Saccharomyces cerevisiae when expressed in these model organisms. Five antitoxin genes, also known as immunity genes, were also identified, which protect the bacteria producing the toxins from self-destruction.
The researchers also found that the toxins exhibit antifungal activity against a range of pathogenic fungi, while leaving certain invertebrate species and macrophages unaffected. The study’s experimental results suggest that these toxins primarily act as efficient enzymes that target essential cellular processes, such as the cell membrane, DNA, or cell division.
Structural analysis of two toxin-immunity protein complexes further confirmed that some of these toxins possess DNase activity, which can degrade DNA in target cells.
“Our findings expand our understanding of how bacteria use toxins in competition with other microbes and provide exciting avenues for future research into critically needed antimicrobial agents against human and plant bacterial and fungal pathogens,” said Levy. “The potential for these toxins to serve as a foundation for new clinical treatments or biotechnological innovations is particularly exciting.”
The discovery could pave the way for novel antimicrobial strategies, particularly with the rise of antibiotic-resistant pathogens. The study has broad implications for both the understanding of microbial interactions in different environments and the development of next-generation antimicrobials.
