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Unlocking Nature’s Secrets: Scientists Discover Antibacterial Compounds in Frogs to Combat Superbugs

Engineers have derived potent new antibiotics from a frog’s secretions. The new molecules demonstrated capabilities on par with existing last-resort antibiotics, without harming human cells or beneficial gut bacteria.

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The world of science has long been fascinated by the unique properties of frogs, which have thrived for hundreds of millions of years in almost every corner of the earth. From tropical jungles to subarctic forests, these amphibians have developed remarkable defenses against the hordes of bacteria that thrive in their moist environments. Now, scientists have unlocked a secret that could change the face of medicine: frogs’ antibacterial compounds.

Researchers from the University of Pennsylvania School of Engineering and Applied Science have discovered novel antibiotics in the secretions of a frog commonly found in South Asia. The study, published in Trends in Biotechnology (Cell Press), builds on previous work from the same lab, which has uncovered antimicrobial compounds in DNA of extinct organisms, including the wooly mammoth, Neanderthals, and even human gut microbiome.

“We’re motivated by imagining environments where evolution would spur the creation of antibiotics,” says Cesar de la Fuente, Presidential Associate Professor in Bioengineering and Chemical and Biomolecular Engineering. “Amphibians live in very microbe-rich environments. They very rarely get infected despite being surrounded by microbes, so they must produce antimicrobial compounds.”

One such compound is Andersonnin-D1, a peptide discovered in the Odorrana andersonii frog. However, this peptide tends to form clumps, increasing the likelihood of toxic side effects and diminishing its efficacy at fighting bacteria. To overcome this limitation, researchers have employed “structure-guided design,” a process that involves minute changes to the peptide’s chemical structure.

After two rounds of structure-guided design, the researchers developed multiple antibiotic candidates without the drawbacks of the unmodified peptide. These new compounds were tested against a range of bacteria in preclinical models and found to be as effective as last-resort antibiotics like polymyxin B.

The study demonstrates that nature has the power to inspire medical innovation. As de la Fuente emphasizes, “We are excited that frogs — and nature in general — can inspire new molecules that could be developed into antibiotics.” If additional preclinical testing goes well, the researchers will submit the peptides for Investigational New Drug (IND) enabling studies, paving the way for clinical trials.

This groundbreaking research was conducted at the University of Pennsylvania School of Engineering and Applied Science, with funding from various organizations, including Procter & Gamble Company, United Therapeutics, and Defense Threat Reduction Agency grants. The findings have significant implications for the development of new antibiotics to combat superbugs, which pose a growing threat to global health.

Bacteria

Unlocking Efficiency: Researchers Reveal Secrets of Cell Division with Min Proteins

The Min protein system prevents abnormal cell division in bacteria, but is poorly understood. Researchers have uncovered how engineered e.coli bacteria control protein levels for maximum efficiency.

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The Min protein system is a complex process that helps bacteria divide evenly and correctly. For decades, scientists have studied this system, but understanding how it works efficiently has been a challenge. Recently, researchers at the University of California San Diego (UCSD) made a groundbreaking discovery that sheds new light on the efficiency of cell division.

The UCSD team developed a way to control Min protein expression levels independently in E. coli cells. This allowed them to observe how different concentrations of Min proteins affect the oscillations between the poles of the cell. The results were surprising: despite varying concentrations, the oscillations remained stable across a wide range, with E. coli producing just the right amount of Min proteins.

This breakthrough is significant because it shows that the Min protein system can efficiently guide division to the correct location without relying on precise control over protein levels. This finding has far-reaching implications for our understanding of cellular organization and function.

The study was published in Nature Physics, a leading scientific journal, and was funded by the National Institutes of Health (NIH). The research team consisted of experts from both physics and chemistry/biochemistry departments at UCSD, highlighting the importance of interdisciplinary collaboration in advancing our knowledge of cellular biology.

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Bacteria

“Unlocking TB Diagnosis: New Molecular Label Could Lead to Simpler, Faster Tests”

Chemists found a way to identify a complex sugar molecule in the cell walls of Mycobacterium tuberculosis, the world’s deadliest pathogen. This labeling could lead to simpler, faster TB tests.

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The world’s deadliest infectious disease, tuberculosis (TB), claims over 1 million lives annually. Despite advancements in diagnosis and treatment, TB remains a significant challenge, particularly in developing nations where access to chest X-rays and molecular diagnostics is limited. Current diagnostic methods often have high false negative rates and require extensive sample preparation, delaying diagnosis.

MIT chemists have developed a breakthrough approach using an organic molecule that reacts with specific sulfur-containing sugars found only in three bacterial species, including Mycobacterium tuberculosis (Mtb), the microbe responsible for TB. By labeling a glycan called ManLAM using this small-molecule tag, researchers can now visualize where it is located within the bacterial cell wall and study what happens to it throughout the first few days of tuberculosis infection.

The research team led by Laura Kiessling, Novartis Professor of Chemistry at MIT, aims to use this approach to develop a diagnostic that could detect TB-associated glycans in culture or urine samples. This would provide a cheaper and faster alternative to existing diagnostics, making it more accessible to developing nations where TB rates are high.

Using their small-molecule sensor instead of antibodies, the researchers hope to create a more sensitive test that can detect ManLAM in the urine even when only small quantities are present. This has significant implications for TB diagnosis and treatment, particularly for patients with very active cases or those who are immunosuppressed due to HIV or other conditions.

The research was funded by the National Institute of Allergy and Infectious Disease, the National Institutes of Health, the National Science Foundation, and the Croucher Fellowship. The findings have the potential to revolutionize TB diagnosis and improve patient outcomes worldwide.

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A Game-Changing ‘Treasure Chest’ for Targeted Gut Treatment: Delivering Medicine Directly to the Lower Gut

A new approach to drug design can deliver medicine directly to the gut in mice at significantly lower doses than current inflammatory bowel disease treatments. The proof-of-concept study introduced a mechanism called ‘GlycoCaging’ that releases medicine exclusively to the lower gut at doses up to 10 times lower than current therapies.

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The discovery of a new approach to drug design, called GlycoCaging, has opened up promising possibilities for targeted treatment of inflammatory bowel disease (IBD) in humans. This innovative technique involves releasing medicine directly into the lower gut at significantly lower doses than current therapies.

Researchers from the University of British Columbia (UBC) have developed this mechanism, which relies on specific bacteria residing in the human gut to unlock the “treasure chest” containing the medicine. By bonding a molecule to a steroid, the researchers have created a system that can deliver potent drugs directly to the inflamed areas of the gut.

According to Dr. Harry Brumer and Dr. Laura Sly, co-senior authors of the study published in Science, this technique has the potential to revolutionize the treatment of IBD, which affects an estimated 322,600 Canadians as of 2023. The current treatments for IBD often come with serious side effects, including osteoporosis, high blood pressure, diabetes, and negative mental health outcomes.

Using mice models of IBD, the researchers demonstrated that GlycoCaging can deliver medicine at doses up to 10 times lower than non-caged versions while achieving the same anti-inflammatory effects. The study showed that the drug was targeted exclusively to the gut, with minimal absorption in other areas of the body.

The potential for human treatment is promising, as the research team found that all people had the ability to activate the drugs using the GlycoCaging system, even those with IBD. Moreover, the majority of participants had genetic markers indicating their ability to use this system.

While more advanced animal trials and human clinical trials are needed to further validate the efficacy and safety of GlycoCaging, this innovative approach has the potential to transform the treatment of IBD and other gut-related disorders. The UBC researchers have patented the technology, paving the way for future development and implementation in humans.

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