In the United States alone, drug-resistant bacteria and fungi infect almost 3 million people per year and kill about 35,000. Antibiotics are essential and effective, but in recent years overuse has led to some bacteria developing resistance to them. The infections are so difficult to treat, the World Health Organization deemed antibiotic resistance a top 10 global public health threat. Now, Professor John E. Moses at Cold Spring Harbor Laboratory (CSHL) has created a new weapon against these drug-resistant superbugs—an antibiotic that can shape-shift by rearranging its atoms. Moses came up with the idea of shape-shifting antibiotics while observing tanks in military training exercises. With rotating turrets and nimble movements, the tanks could respond quickly to possible threats.

A few years later, Moses learned of a molecule called bullvalene. Bullvalene is a fluxional molecule, meaning its atoms can swap positions. This gives it a changing shape with over a million possible configurations—exactly the fluidity Moses was looking for. Several bacteria, including MRSA, VRSA, and VRE, have developed resistance to a potent antibiotic called vancomycin, used to treat everything from skin infections to meningitis. Moses thought he could improve the drug’s bacteria-fighting performance by combining it with bullvalene. He turned to click chemistry, a Nobel Prize–winning class of fast, high-yielding chemical reactions that “click” molecules together reliably. This makes the reactions more efficient for wide-scale use.

“Click chemistry is great,” says Moses, who studied this revolutionary development under two-time Nobel laureate K. Barry Sharpless. “It gives you certainty and the best chance you’ve got of making complex things.”

Using this technique, Moses and his colleagues created a new antibiotic with two vancomycin “warheads” and a fluctuating bullvalene center. Moses tested the new drug in collaboration with Dr. Tatiana Soares da-Costa (University of Adelaide). The researchers gave the drug to VRE-infected wax moth larvae, which are commonly used to test antibiotics. They found the shape-shifting antibiotic significantly more effective than vancomycin at clearing the deadly infection. Additionally, the bacteria didn’t develop resistance to the new antibiotic.

Researchers can use click chemistry with shape-shifting antibiotics to create a multitude of new drugs, Moses explains. Such weapons against infection may even be key to our species’ survival and evolution. “If we can invent molecules that mean the difference between life and death,” he says, “that’d be the greatest achievement ever.”

Source: https://www.cshl.edu/

Cannabidiol (CBD), the main nonpsychoactive ingredient of the cannabis plant, can kill Gram-positive bacteria and, more impressively, Gram-negative bacteria, which excel at antibiotic resistance because they enjoy an extra layer of protection, an outer cell membrane. The ability of CBD to slay Gram-negative bacteria is a new finding, one reported by a team of scientists in Australia. According to the scientists, CBD analogs could constitute the first new class of antibiotics against Gram-negative bacteria that has been developed since the 1960s.

The new finding appeared in the journal Communications Biology, in an article titled, “The antimicrobial potential of cannabidiol.” According to this article, CBD not only killed Gram-positive bacteria such as highly resistant Staphylococcus aureus, Streptococcus pneumoniae, and Clostridioides difficile, it also showed potency against the Gram-negative bacteria Neisseria gonorrhoeae, Neisseria meningitides, Moraxella catarrhalis, and Legionella pneumophila. These Gram-negative bacteria are responsible for sexually transmitted gonorrhea, life-threatening meningitis, airway infections (such as bronchitis and pneumonia), and Legionnaires’ disease, respectively.

“Our results demonstrate that cannabidiol has excellent activity against biofilms, little propensity to induce resistance, and topical in vivo efficacy,” the authors of the article wrote. “Multiple mode-of-action studies point to membrane disruption as cannabidiol’s primary mechanism.”

The authors included scientists from the University of Queensland in Australia and Botanix Pharmaceuticals. At the University of Queensland’s Centre for Superbug Solutions, scientists led by associate professor Mark Blaskovich, PhD, mimicked a two-week patient treatment in laboratory models to see how fast the bacteria mutated to try to outwit CBD’s killing power.

“Cannabidiol showed a low tendency to cause resistance in bacteria even when we sped up potential development by increasing concentrations of the antibiotic during ‘treatment,’” said Blaskovich, the corresponding author of the article in Communications Biology. “We think that cannabidiol kills bacteria by bursting their outer cell membranes, but we don’t know yet exactly how it does that, and we need to do further research.”

Source: https://www.genengnews.com/