Nav: Home

Stanford researchers synthesize healing compounds in scorpion venom

June 10, 2019

A scorpion native to Eastern Mexico may have more than just toxin in its sting. Researchers at Stanford University and in Mexico have found that the venom also contains two color-changing compounds that could help fight bacterial infections.

The team not only isolated the compounds in the scorpion's venom, but also synthesized them in the lab and verified that the lab-made versions killed staphylococcus and drug-resistant tuberculosis bacteria in tissue samples and in mice.

The findings, published in the June 10 issue of the journal Proceedings of the National Academy of Sciences, highlight the potential pharmacological treasures awaiting discovery in the toxins of scorpions, snakes, snails and other poisonous creatures.

"By volume, scorpion venom is one of the most precious materials in the world. It would costs $39 million to produce a gallon of it," said study senior author Richard Zare, who led the Stanford group. "If you depended only on scorpions to produce it, nobody could afford it, so it's important to identify what the critical ingredients are and be able to synthesize them."

Milking scorpions

Zare worked with his colleagues in Mexico, including Lourival Possani, a professor of molecular medicine at the National University of Mexico, whose students caught specimens of the scorpion Diplocentrus melici for study.

"The collection of this species of scorpion is difficult because during the winter and dry seasons, the scorpion is buried," Possani said. "We can only find it in the rainy season."

For the past 45 years, Possani has focused on identifying compounds with pharmacological potential in scorpion venom. His group has previously uncovered potent antibiotics, insecticides and anti-malarial agents hidden in the arachnid's poison.

When the Mexican researchers milked the venom of D. melici - a process that involves stimulating the tail with mild electrical pulses - they noticed that the venom changed color, from clear to brownish, when it was exposed to air.

When Possani and his lab investigated this unusual color-change, they found two chemical compounds that they believed were responsible. One of the compounds turned red when exposed to air, while the other turned blue.

To find out more about each compound, Possani reached out to Zare's group at Stanford, which has a reputation for identifying and synthesizing chemicals.

Using only a tiny sample of the venom, Stanford postdoctoral researchers Shibdas Banerjee and Gnanamani Elumalai were able to work out the molecular structure of the two compounds. "We only had 0.5 microliters of the venom to work with," said Zare, who is the Marguerite Blake Wilbur Professor in Natural Science at Stanford's School of Humanities and Sciences. "This is ten times less than the amount of blood a mosquito will suck in a single serving."

Using clues gleaned from running the compounds through various chemical analysis techniques, the Stanford scientists concluded that the color-changing ingredients in the venom were two previously unknown benzoquinones - a class of ring-like molecules known to have antimicrobial properties.

The benzoquinones in the scorpion venom appeared to be nearly identical to one another. "The two compounds are structurally related, but whereas the red one has an oxygen atom on one of its branches, the blue one has a sulfur atom," Banerjee said.

The group confirmed the compounds' structures when, through much trial and error, they learned how to synthesize them. "Many of the reactions you write on paper that appear to work don't actually work when you try them in the lab, so you need to be patient and have many different ideas," said Stanford MD-PhD graduate student Shyam Sathyamoorthi, who led the synthesis efforts.

Drug potential

Zare's lab sent a batch of the newly synthesized benzoquinones to Rogelio Hernández-Pando, a pathologist at the Salvador Zubirán National Institute of Health Sciences and Nutrition in Mexico City, whose group tested the lab-made compounds for biological activity.

Hernández-Pando's group found that the red benzoquinone was particularly effective at killing the highly infectious staphylococcus bacteria, while the blue one was lethal to both normal and multi-drug-resistant strains of tuberculosis-causing bacteria.

"We found that these compounds killed bacteria, but then the question became 'Will it kill you, too?'" Zare said. "And the answer is no: Hernández-Pando's group showed that the blue compound kills tuberculosis bacteria but leaves the lining of the lungs in mice intact."

Possani said the antimicrobial properties of the compounds might not have been discovered if Zare's group had not figured out how to synthesize it, thus allowing it to be produced in larger quantities. "The amount of venom components we can get from the animals is extremely low," Possani said. "The synthesis of the compounds was decisive for the success of this work."

The Stanford and Mexican scientists are planning further collaborations to determine whether the isolated venom compounds can be transformed into drugs and also why they're present in the venom in the first place.

"These compounds might not be the poisonous component of the venom," Zare said. "We have no idea why the scorpion makes these compounds. There are more mysteries."
-end-
Zare is also a member of Stanford Bio-X, the Wu Tsai Neurosciences Institute and the Stanford Woods Institute for the Environment, as well as a faculty fellow at Stanford ChEM-H.

The Stanford work was supported by the Air Force Office of Scientific Research.

Stanford University -- School of Humanities and Sciences

Related Tuberculosis Articles:

Blocking the iron transport could stop tuberculosis
The bacteria that cause tuberculosis need iron to survive. Researchers at the University of Zurich have now solved the first detailed structure of the transport protein responsible for the iron supply.
Tuberculosis: New insights into the pathogen
Researchers at the University of Würzburg and the Spanish Cancer Research Centre have gained new insights into the pathogen that causes tuberculosis.
Unmasking the hidden burden of tuberculosis in Mozambique
The real burden of tuberculosis is probably higher than estimated, according to a study on samples from autopsies performed in a Mozambican hospital.
HIV/tuberculosis co-infection: Tunneling towards better diagnosis
1.2 million people in the world are co-infected by the bacteria which causes tuberculosis and AIDS.
Reducing the burden of tuberculosis treatment
A research team led by MIT has developed a device that can lodge in the stomach and deliver antibiotics to treat tuberculosis, which they hope will make it easier to cure more patients and reduce health care costs.
Tuberculosis: Commandeering a bacterial 'suicide' mechanism
The bacteria responsible for tuberculosis can be killed by a toxin they produce unless it is neutralized by an antidote protein.
A copper bullet for tuberculosis
Tuberculosis is a sneaky disease, and the number one cause of death from infectious disease worldwide.
How damaging immune cells develop during tuberculosis
Insights into how harmful white blood cells form during tuberculosis infection point to novel targets for pharmacological interventions, according to a study published in the open-access journal PLOS Pathogens by Valentina Guerrini and Maria Laura Gennaro of Rutgers New Jersey Medical School, and colleagues.
How many people die from tuberculosis every year?
The estimates for global tuberculosis deaths by the World Health Organisation (WHO) and the Institute for Health Metrics and Evaluation (IHME) differ considerably for a dozen countries, according to a study led by ISGlobal.
Beyond killing tuberculosis
Historically, our view of host defense against infection was that we must eliminate pathogens to eradicate disease.
More Tuberculosis News and Tuberculosis Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Teaching For Better Humans 2.0
More than test scores or good grades–what do kids need for the future? This hour, TED speakers explore how to help children grow into better humans, both during and after this time of crisis. Guests include educators Richard Culatta and Liz Kleinrock, psychologist Thomas Curran, and writer Jacqueline Woodson.
Now Playing: Science for the People

#556 The Power of Friendship
It's 2020 and times are tough. Maybe some of us are learning about social distancing the hard way. Maybe we just are all a little anxious. No matter what, we could probably use a friend. But what is a friend, exactly? And why do we need them so much? This week host Bethany Brookshire speaks with Lydia Denworth, author of the new book "Friendship: The Evolution, Biology, and Extraordinary Power of Life's Fundamental Bond". This episode is hosted by Bethany Brookshire, science writer from Science News.
Now Playing: Radiolab

Space
One of the most consistent questions we get at the show is from parents who want to know which episodes are kid-friendly and which aren't. So today, we're releasing a separate feed, Radiolab for Kids. To kick it off, we're rerunning an all-time favorite episode: Space. In the 60's, space exploration was an American obsession. This hour, we chart the path from romance to increasing cynicism. We begin with Ann Druyan, widow of Carl Sagan, with a story about the Voyager expedition, true love, and a golden record that travels through space. And astrophysicist Neil de Grasse Tyson explains the Coepernican Principle, and just how insignificant we are. Support Radiolab today at Radiolab.org/donate.