Soil Bacteria Use Umbrella Toxins to Fight Back

Scientists have found that soil bacteria called Streptomyces secrete toxic protein particles in the shape of umbrellas that are meant to suppress competitors, particularly those that belong to their species.

The discovery of the umbrella toxin particles and details regarding their composition, structure, and mode of action were published in Nature.

The umbrella toxin proteins are the most recent example of the diverse attacks these bacteria have launched on their microscopic competitors. Their densely populated, multifarious bacterial communities are a flurry of antimicrobial assaults, retaliatory attacks, and defense mechanisms.

Ironically, a lot of antibiotics that are used in clinical settings either directly come from or are modeled after molecules that bacteria naturally fight one another. The chemical arsenal that streptomyces use to outgun their rivals is one of the best sources of these molecules. One of them is the widely used, all-purpose medication streptomycin.

These recently discovered antibacterial toxins are distinct from the small-molecule antibiotics produced by Streptomyces because they are large complexes made up of several proteins. When it comes to the bacteria they target, they are also far more specific than small-molecule antibiotics.

The authors hypothesize that these characteristics of umbrella toxins account for their escape from detection during over a century of studies on toxins generated by Streptomyces.

Bioinformatics search for novel bacterial toxins turned up genes encoding umbrella toxins. These toxins form a large complex with other proteins, according to research conducted by Qinqin Zhao in the microbiology lab of Joseph Mougous at the University of Washington School of Medicine. The experiments were genetic and biochemical.

Young Park conducted cryo-electron microscopy on these protein complexes in the lab of David Veesler, a Howard Hughes Medical Institute Investigator and Professor of Biochemistry at the UW School of Medicine.

According to these investigations, Qinqin's isolated toxin complexes take on a remarkable appearance consistent with their discovery in Seattle. They resemble umbrellas.

The shape of these particles is quite peculiar, and it will be interesting in future work to learn how their unusual morphology helps them eliminate target bacteria.”

Joseph Mougous, Professor, Department of Microbiology, University of Washington School of Medicine

Joseph Mougous is a Howard Hughes Medical Investigator.

Using a wide range of organisms, including fungi and 140 distinct bacteria, some of which were extracted from sorghum plants grown in the lab of study author Devin Coleman at the University of California, Berkeley, and the US Department of Agriculture Agricultural Research Service, the scientists then attempted to identify the targets of these toxins.

The toxins particularly targeted other Streptomyces species, which are among these possible adversaries.

We think this exquisite specificity may be due to the proteins that make up the spokes of the umbrella, which vary across the particles. These include proteins that might latch onto specific sugars found on the surface of competitor bacteria.”

S. Brook Peterson, Senior Scientist and Study Author, University of Washington School of Medicine

Study authors Dapeng Zhang of St. Louis University and his graduate student Youngjun Tan discovered that many other species of bacteria also possess the genes to produce umbrella particle toxins by examining the thousands of publicly available bacterial genomes. Fascinatingly, every one of these species forms branching filaments, which is an uncommon way for bacteria to grow.

Apart from the numerous unanswered questions regarding the fundamental biology of umbrella toxin particles, Mougous and associates are fascinated by their possible therapeutic uses.

They believe that umbrella toxins may be able to affect the bacteria that cause diphtheria and tuberculosis. It is noted that the bacteria in question have developed resistance to conventional antibiotics. The scientists hypothesized that they might be worth investigating because umbrella toxin particles can suppress these dangerous disease-causing bacteria.

Source:
Journal reference:

Zhao, Q., et al. (2024) Streptomyces umbrella toxin particles block hyphal growth of competing species. Nature. doi.org/10.1038/s41586-024-07298-z

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