Scorpion venom contains compounds that could help fight Staph bacteria and tuberculosis

Researchers from Stanford University and the National Autonomous University of Mexico (UNAM) have discovered that a scorpion discovered in eastern Mexico had a venom that could have antibacterial properties.

The results of their study on the venom of the Mexican scorpion species Diplocentrus melici have been published in the journal Proceedings of the National Academy of Sciences this week. The study was titled "Antimicrobial agents containing 1,4-benzoquinone against Staphylococcus aureus and Mycobacterium tuberculosis derived from the scorpion venom. "

The research team focused on isolating the compounds in the scorpion venom and synthesizing them in the laboratory to produce synthetic chemical versions of the venom. Their results revealed that both natural venom and synthetic venom were able to kill bacteria such as Staphylococcus and drug-resistant strains of TB bacteria in mice.

Antimicrobial resistance is a growing problem around the world. Due to the lack of new antimicrobials and increasing resistance, common bacterial infections may soon be life threatening as no available antimicrobials could work against them. Researchers are studying toxin-like solutions of snakes, scorpions, snails and poisonous animals to look for new agents against drug-resistant bacteria.

Lead author Richard Zare, head of the Stanford team in Stanford University's Department of Chemistry, and Margaret Blake Wilbur Professor of Natural Sciences in the Faculty of Human Sciences at Stanford University, said in a statement: "The volume most precious materials in the world. It would cost $ 39 million to produce a gallon. If you only depend on scorpions to produce it, no one can pay you for it, so it is important to determine what the essential ingredients are and to be able to synthesize them. "

For example, the Stanford team collaborated with Mexican colleagues led by Professor Lourival Possani, Department of Molecular Medicine, National University of Mexico. The Mexican team collected specimens of the scorpion Diplocentrus melici to study. Possani said: "The collection of this species of scorpion is difficult because during the winter and the dry season, the scorpion is buried. We can only find it during the rainy season. Possani has been working for 45 years on the pharmacological properties of the venom of this scorpion. He and his team discovered the insecticidal and antimalarial properties of this venom.

The Mexican team used light electrical impulses applied to the tail of the scorpions D. melici and found that this led to the trafficking of venom that could be collected. They noted that when the venom was extracted, the color changed from light to brownish. The team then examined the chemical composition of the venom and discovered that it contained two chemical compounds. One of these chemicals became red while the other became blue when it was exposed to air. Possani's team then approached the Stanford team to identify the chemicals and synthesize them in the lab.

Zare's postdoctoral researchers Shibdas Banerjee and Gnanamani Elumalai used a small sample and successfully decoded the molecular structure of the venom. Zare said: "We had only 0.5 microliters of venom to work with. That's ten times less than the amount of blood that a mosquito will suck in one portion. The team discovered that the color-changing chemicals were benzoquinones, known for their antimicrobial properties. Banerjee explained, "The two compounds are structurally related, but while red has an oxygen atom on one of its branches, blue has a sulfur atom." The authors write, "The red compound was determined to be 3,5-dimethoxy-2- (methylthio) cyclohexa-2,5-diene-1,4-dione, and the blue compound was determined to be 5-methoxy- 2,3-bis (methylthio) cyclohexa-2,5-diene-1,4-dione.

Shyam Sathyamoorthi, a Ph.D. student at Stanford MD, led the next step in the process – the synthesis of venom in the lab. He said, "Many of the reactions you write on paper that seem to work do not work when you test them in the lab. So you have to be patient and have many different ideas. "The team was finally able to synthesize the results. benzoquinones.

These samples were then sent to pathologist Rogelio Hernández-Pando of the Salvador Zubirán National Institute of Health Sciences and Nutrition in Mexico City. His team and he tested the synthetic sample on laboratory mice to check their biological activity. The team found that the red chemical kills staphylococcal bacteria, while blue was able to kill TB bacteria sensitive to or resistant to conventional anti-tuberculosis drugs. Zare explained that the important question was whether these compounds were also deadly to mice. The results of laboratory studies, however, showed that the compound was safe for healthy tissues of mice infected with the bacterium but killing only the bacteria. Zare said: "The Hernández-Pando group has shown that the blue compound kills the TB bacteria but leaves intact the lining of the lungs of the mice."

Possani said that venom synthesis in the laboratory was the key to the success of this experiment. He explained: "The amount of venom components that we can get from animals is extremely small. The synthesis of the compounds was decisive for the success of this work. "

In a next step, both teams will work to transform venom into drugs that can help treat drug-resistant bacterial infections.

Zare said in conclusion: "These compounds might not be the toxic component of venom," said Zare. "We have no idea why the scorpion makes these compounds. There are more mysteries.