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Antibiotics Synthesized from Scorpion Venom

(Andrey Barsukov, Pixabay)

11 June 2019. Biochemistry labs in the U.S. and Mexico isolated and synthesized key compounds from scorpion venom that kills bacteria resistant to antibiotics. A team from Stanford University in California and 2 institutions in Mexico report their findings in yesterday’s issue of Proceedings of the National Academy of Sciences (paid subscription required).

The lab of Lourival Possani at the Institute of Biotechnology at National University of Mexico in Morelos studies therapeutic derivatives from the venom of scorpions indigenous to Mexico. One species of scorpion, the Diplocentrus melici, is not studied as often since it lives underground most of the year, appearing only in Mexico’s rainy season. Tests of the venom from this species of scorpion show the venom changes color, from clear to brown, when exposed to air. An analysis of the venom reveals 2 compounds in the benzoquinone family likely responsible for the color change, one red in color and the other blue.

The Possani lab was able to extract only tiny amounts of the chemicals from the scorpion venom, and called in Stanford chemistry professor Richard Zare to synthesize the compounds and analyze them further. Among the Zare lab’s specialties is the analysis of compounds in very small quantities, as in the case of the chemicals derived from Possani’s scorpion. “We only had 0.5 microliters of the venom to work with,” says Zare in a Stanford University statement. “This is 10 times less than the amount of blood a mosquito will suck in a single serving.”

Stanford postdoctoral researchers Shibdas Banerjee — now at Indian Institute of Science Education and Research in Tirupati —  and Gnanamani Elumalai conducted sophisticated analytical tests on the venom chemicals. These techniques used mass spectrometry that subjects the compounds to electric currents and magnetic fields, and nuclear magnetic resonance spectroscopy that determines the structure of organic compounds.

This analysis enabled the team to identify the precise chemical composition of the benzoquinone compounds, and after some trial-and-error developed synthetic versions of the compounds in greater quantities. Benzoquinones are known to have antimicrobial properties, and the researchers recruited pathologist Rogelio Hernández-Pando at Salvador Zubirán National Institute of Health Sciences and Nutrition in Mexico City for further testing as possible antibiotics.

In lab cultures, Hernández-Pando and colleagues found the red benzoquinone effective against Staphylococcus aureus bacteria. Staphylococcus aureus are found in health care settings and include the multi-drug resistant strain of Methicillin-resistant Staphylococcus aureus, or MRSA bacteria. The researchers found blue benzoquinone effective against Mycobacterium tuberculosis bacteria responsible for tuberculosis, also including multi-drug resistant strains.

The Hernández-Pando lab then tested the blue benzoquinone on lab mice induced with multi-drug resistant tuberculosis infections. After 2 months, the mice treated with blue benzoquinone had lower bacterial levels and less lung tissue damage. And healthy mice treated with blue benzoquinone did not show adverse effects from the compound.

The U.S. and Mexican researchers plan to continue their work on these compounds to further determine their potential as therapies, but also to better understand more basic questions about the chemicals. “These compounds might not be the poisonous component of the venom,” says Zare, adding, “We have no idea why the scorpion makes these compounds.”

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