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Umbrella toxin discovery may help human antibiotic resistance

For nearly a hundred years, the soil bacteria Streptomyces has been a goldmine for antibiotic discovery, yet it still harbored a secret — umbrella toxin particles.

These intriguing toxic proteins, which remarkably resemble the shape of an umbrella, were only recently uncovered after being overlooked for a century.

This discovery sheds light on the aggressive tactics Streptomyces employs to defend against, and dominate, its microbial neighbors.

Umbrella toxin particles

The research, published in Nature, describes the structure, composition, and function of the umbrella toxin particles. These toxins are named for their structural resemblance to an umbrella, a feature that distinguishes them visually and functionally from other microbial agents.

The structure of umbrella toxins is complex, comprising multiple protein components that assemble into a formation reminiscent of an umbrella. This includes a “cap” and “spokes,” which are thought to be critical for their function and specificity.

Unlike typical antibiotics produced by Streptomyces that are smaller molecules, umbrella toxins are large, multi-protein complexes. Their specificity in targeting certain bacteria sets them apart from the broad-spectrum antibiotics like streptomycin.

In the study, the detailed architecture of these proteins was revealed through advanced techniques such as cryo-electron microscopy. Umbrella toxins represent a new class of antimicrobial agents derived from the complex interactions within microbial communities.

Microbial weapons using umbrella toxins

The discovery of the umbrella toxins is a glimpse into the fierce competition among microbes in soil. Additionally, these bacteria reside in densely packed communities.

They are constantly engaged in a battle for survival, deploying an arsenal of antimicrobial substances. Interestingly, many antibiotics used in clinics today originate from these microbial weapons.

Bioinformatics unveil umbrella toxins

The journey to this discovery began with a bioinformatics search that led to the identification of genes encoding these toxins.

Qinqin Zhao and the team from Joseph Mougous’ microbiology lab at the University of Washington School of Medicine conducted biochemical and genetic experiments to uncover the role of these proteins.

Cryo-electron microscopy studies by Young Park, under the guidance of David Veesler, further illustrated that these proteins assemble into complexes resembling umbrellas — a fitting discovery for researchers based in Seattle.

Properties of umbrella toxins

Joseph Mougous, a professor of microbiology and an investigator at the Howard Hughes Medical Institute (HHMI), noted the peculiar shape of these particles. Intriguingly, these toxins are highly specific. They primarily target other Streptomyces species.

“We think this exquisite specificity may be due to the proteins that make up the spokes of the umbrella, which vary across the particles,” explained S. Brook Peterson, a senior scientist in the Mougous lab.

These proteins potentially latch onto specific sugars on the surfaces of competitor bacteria, allowing for targeted attacks.

Clinical potential

Further investigation by Dapeng Zhang from St. Louis University, alongside his graduate student Youngjun Tan, has expanded our understanding of umbrella toxins.

Their research found that the genes encoding these unique toxins are widespread among various bacteria. This is particularly significant in bacteria that exhibit branching filament growth, a rare trait that adds a layer of complexity to their biological functions.

The clinical implications of these findings are substantial. As pathogens responsible for severe diseases like tuberculosis and diphtheria increasingly resist current antibiotics, the discovery of umbrella toxins offers a promising new avenue for treatment.

These toxins’ ability to target specific bacteria with precision could revolutionize how we develop antibiotics, potentially leading to more effective therapies against resistant strains.

This breakthrough paves the way for novel medical strategies that could significantly impact public health by providing targeted, potent solutions to combat stubborn bacterial infections.

A new frontier in antibiotic research

The discovery of umbrella toxin particles opens a new chapter in the quest for novel antimicrobial strategies. It enhances our understanding of microbial warfare and holds promise for developing new therapeutic agents to tackle some of the toughest bacterial infections.

As research continues, the implications of this discovery could reach far beyond the confines of microbiological labs, potentially ushering in a new era of antibiotic development.

The full study was published in the journal Nature.


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