The toxins are like an umbrella and can stop the growth of similar bacteria. They come from Streptomyces. Image: Angela Gao
Scientists have found umbrella-shaped proteins that can attack and kill certain bacteria, offering hope for treating resistant infections.
Researchers have found toxic protein particles, shaped like umbrellas, in soil bacteria known as Streptomyces , which they use to defeat other bacteria, especially those of the same species.
The discovery of these umbrella toxin particles and information about their structures, composition, and how they work were published on April 17 in the journal Nature.
These umbrella toxin proteins are just one example of how these bacteria attack other microorganisms. The bacteria communities where they live are full of antimicrobial attacks, counterattacks, and defenses.
Antibiotics and Bacterial Conflict
Interestingly, many antibiotics used in medicine are derived from or inspired by molecules that bacteria use against each other in nature. The chemical weapons used by Streptomyces against other bacteria are a major source of these molecules, including the commonly used drug streptomycin. A key difference with these new antibacterial toxins is that, unlike the small-molecule antibiotics made by Streptomyces, umbrella toxins are large complexes made of multiple proteins. They are also more specific in the bacteria they target compared to small-molecule antibiotics.
The authors of the paper think that these properties of umbrella toxins explain why they were not discovered during over 100 years of research on toxins made by Streptomyces.
Insights from Bioinformatics and Cryo-Electron Microscopy Nature Genes that make umbrella toxins were found using bioinformatics to search for new bacterial toxins. Scientists discovered that these toxins combine with other proteins to form a large complex through biochemical and genetic experiments conducted by Qinqin Zhao in Joseph Mougous’ microbiology lab at the University of Washington School of Medicine. Young Park, from the lab of David Veesler, a biochemistry professor at the UW School of Medicine and an Investigator of the Howard Hughes Medical Institute, used cryo-electron microscopy to study these protein complexes.
Studies showed that the toxin complexes Qinqin isolated have an interesting shape that looks like umbrellas, which matches their discovery location in Seattle.
A Distinctive Structure and Specificity
Mougous, a microbiology professor at the UW School of Medicine and a Howard Hughes Medical Investigator, said, “The shape of these particles is quite unusual, and it will be interesting to learn in future work how their unique shape helps them eliminate target bacteria.”
The scientists then tried to find out what these toxins target by testing their effects on various organisms, including fungi and 140 different bacteria, some of which were obtained from sorghum plants in the lab of study author Devin Coleman at the University of California-Berkeley and the U.S. Department of Agriculture Agricultural Research Service.
Among these potential enemies, the toxins specifically targeted their own kind: other
Streptomyces
“We believe this fine detail in targeting may be because of the proteins that form the spokes of the umbrella, which differ among the particles. These proteins may attach to specific sugars on the surface of competing bacteria,” said S. Brook Peterson, a senior scientist in the Mougous lab.
After examining many publicly available bacterial genomes, study authors Dapeng Zhang of St. Louis University and his graduate student Youngjun Tan discovered that many other types of bacteria also have the genes to produce umbrella particle toxins. Interestingly, these species all develop branching filaments, a unique mode of growth among bacteria. Potential Clinical Uses and Wider Implications species.
Apart from the numerous unresolved questions about the basic biology of umbrella toxin particles, Mougous and his colleagues are fascinated by their potential medical applications.
They believe that the bacteria causing tuberculosis and diphtheria may be vulnerable to umbrella toxins. They note that these same bacteria have become resistant to traditional antibiotics. The scientists suggested that investigating umbrella toxin particles for their potential to control these serious disease-causing bacteria could be worthwhile.
Reference: “
Streptomyces
umbrella toxin particles block hyphal growth of competing species” by Qinqin Zhao, Savannah Bertolli, Young-Jun Park, Yongjun Tan, Kevin J. Cutler, Pooja Srinivas, Kyle L. Asfahl, Citlali Fonesca-García, Larry A. Gallagher, Yaqiao Li, Yaxi Wang, Devin Coleman-Derr, Frank DiMaio, Dapeng Zhang, S. Brook Peterson, David Veesler and Joseph D. Mougous, 17 April 2024,
DOI: 10.1038/s41586-024-07298-zThe study was supported by the Microbial Interactions & Microbiome Center at the University of Washington, which Mougous directs as the holder of the Lynn M. and Michael D. Garvey Endowed Chair in Gastroenterology. The goal of mim_c is to catalyze microbiome research in the Pacific Northwest, with an emphasis on defining the molecular mechanisms of interbacterial interactions underlying microbial communities important to human health or the environment. The study of umbrella toxin particles was also funded by the Defense Advanced Research Projects Agency Biological Technology Program: Harnessing Enzymatic Activity for Lifesaving Remedies (9HR0011-21-0012), the National Institute of Allergy and Infectious Diseases (75N93022C00036), a Pew Medical Scholars Program, an Investigators in the Pathogenesis of Infectious Disease Award from the Burroughs Wellcome Fund, the UW Arnold and Mabel Beckman cryo-EM Center, the National Institutes of Health S100DO32290, Saint Louis University Startup Fund, the U.S. Department of Agriculture (CRIS 2030-21430-0080OD), and the USDA-NIFA (2019-67019-29306). The study is a contribution of the Pacific Northwest National Laboratory Secure Biosystems Design Focus Area: Persistence Control Engineered Functions in Complex Soil Microbiomes (U.S. Department of Energy contract DE-AC05-76RL01830). Nature.
Scientists have found proteins that are shaped like umbrellas and can target and eliminate particular bacteria. This could be a hopeful solution for treating infections that are resistant to treatment. Researchers have found harmful protein particles that have an umbrella-like shape,…
The study was supported by the Microbial Interactions & Microbiome Center at the University of Washington, which Mougous directs as the holder of the Lynn M. and Michael D. Garvey Endowed Chair in Gastroenterology. The goal of mim_c is to catalyze microbiome research in the Pacific Northwest, with an emphasis on defining the molecular mechanisms of interbacterial interactions underlying microbial communities important to human health or the environment.
The study of umbrella toxin particles was also funded by the Defense Advanced Research Projects Agency Biological Technology Program: Harnessing Enzymatic Activity for Lifesaving Remedies (9HR0011-21-0012), the National Institute of Allergy and Infectious Diseases (75N93022C00036), a Pew Medical Scholars Program, an Investigators in the Pathogenesis of Infectious Disease Award from the Burroughs Wellcome Fund, the UW Arnold and Mabel Beckman cryo-EM Center, the National Institutes of Health S100DO32290, Saint Louis University Startup Fund, the U.S. Department of Agriculture (CRIS 2030-21430-0080OD), and the USDA-NIFA (2019-67019-29306). The study is a contribution of the Pacific Northwest National Laboratory Secure Biosystems Design Focus Area: Persistence Control Engineered Functions in Complex Soil Microbiomes (U.S. Department of Energy contract DE-AC05-76RL01830).
