New research reveals that fluorous lipopetides act as highly effective antibiotics.
Bacterial infections resistant to multiple drugs, which no existing antibiotics can treat, represent a significant worldwide challenge. A research group from China has presented a new strategy for creating innovative antibiotics aimed at combating these resistant bacteria in the journal Angewandte Chemie. This approach utilizes protein components combined with fluorous lipid chains to develop the drugs.
Antibiotics are often prescribed far too readily. In many countries, they are distributed without prescriptions and administered in factory farming: prophylactically to prevent infections and enhance performance. As a result, resistance is on the rise—increasingly against reserve antibiotics as well. The development of innovative alternatives is essential.
Learning from Microbes
It is possible to learn some lessons from the microbes themselves. Lipoproteins, small protein molecules with fatty acid chains, are widely used by bacteria in their battles against microbial competitors. A number of lipoproteins have already been approved for use as drugs. The common factors among the active lipoproteins include a positive charge and an amphiphilic structure, meaning they have segments that repel fat and others that repel water. This allows them to bind to bacterial membranes and pierce through them to the interior.
A team led by Yiyun Cheng at East China Normal University in Shanghai aims to amplify this effect by replacing hydrogen atoms in the lipid chain with fluorine atoms. These make the lipid chain simultaneously water-repellant (hydrophobic) and fat-repellant (lipophobic). Their particularly low surface energy strengthens their binding to cell membranes while their lipophobicity disrupts the cohesion of the membrane.
Synthesis and Screening of Fluorous Lipopeptides
The team synthesized a spectrum (substance library) of fluorous lipopeptides from fluorinated hydrocarbons and peptide chains. To link the two pieces, they used the amino acid cysteine, which binds them together via a disulfide bridge. The researchers screened the molecules by testing their activity against methicillin-resistant Staphylococcus aureus (MRSA), a widespread, highly dangerous strain of bacteria that is resistant to nearly all antibiotics. The most effective compound they found was “R6F”, a fluorous lipopeptide made of six arginine units and a lipid chain made of eight carbon and thirteen fluorine atoms. To increase biocompatibility, the R6F was enclosed within phospholipid nanoparticles.
In mouse models, R6F nanoparticles were shown to be very effective against sepsis and chronic wound infections by MRSA. No toxic side effects were observed. The nanoparticles seem to attack the bacteria in several ways: they inhibit the synthesis of important cell-wall components, promoting collapse of the walls; they also pierce the cell membrane and destabilize it; disrupt the respiratory chain and metabolism; and increase oxidative stress while simultaneously disrupting the antioxidant defense system of the bacteria. In combination, these effects kill the bacteria—other bacteria as well as MRSA. No resistance appears to develop.
These insights provide starting points for the development of highly efficient fluorous peptide drugs to treat multi-drug resistant bacteria.
Reference: “A Fluorous Peptide Amphiphile with Potent Antimicrobial Activity for the Treatment of MRSA-induced Sepsis and Chronic Wound Infection” by Jingjing Hu, Nan Liu, Qianqian Fan, Yunqing Gu, Sijia Chen, Fang Zhu and Yiyun Cheng, 23 February 2024, Angewandte Chemie International Edition.
DOI: 10.1002/anie.202403140
The study was funded by the National Key Research and Development Program of China, the National Natural Science Foundation of China, and the Science and Technology Commission of Shanghai Municipality.
News
The Unresolved Puzzle of Long COVID: 30% of Young People Still Suffer After Two Years
A UCL study found that 70% of young people with long Covid recovered within 24 months, but recovery was less likely among older teenagers, females, and those from deprived backgrounds. Researchers emphasized the need [...]
Needle-Free: New Nano-Vaccine Effective Against All COVID-19 Variants
A new nano-vaccine developed by TAU and the University of Lisbon offers a needle-free, room-temperature-storable solution against COVID-19, targeting all key variants effectively. Professor Ronit Satchi-Fainaro’s lab at Tel Aviv University’s Faculty of Medical and [...]
Photoacoustic PDA-ICG Nanoprobe for Detecting Senescent Cells in Cancer
A study in Scientific Reports evaluated a photoacoustic polydopamine-indocyanine green (PDA-ICG) nanoprobe for detecting senescent cells. Senescent cells play a role in tumor progression and therapeutic resistance, with potential adverse effects such as inflammation and tissue [...]
How Dysregulated Cell Signaling Causes Disease
Cell signaling is crucial for cells to communicate and function correctly. Disruptions in these pathways, caused by genetic mutations or environmental factors, can lead to uncontrolled cell growth, improper immune responses, or errors in [...]
Scientists Develop Super-Strong, Eco-Friendly Plastic That Bacteria Can Eat
Researchers at the Weizmann Institute have developed a biodegradable composite material that could play a significant role in addressing the global plastic waste crisis. Billions of tons of plastic waste clutter our planet. Most [...]
Building a “Google Maps” for Biology: Human Cell Atlas Revolutionizes Medicine
New research from the Human Cell Atlas offers insights into cell development, disease mechanisms, and genetic influences, enhancing our understanding of human biology and health. The Human Cell Atlas (HCA) consortium has made significant [...]
Bioeconomic Potential: Scientists Just Found 140 Reasons to Love Spider Venom
Researchers at the LOEWE Centre for Translational Biodiversity Genomics (TBG) have discovered a significant diversity of enzymes in spider venom, previously overshadowed by the focus on neurotoxins. These enzymes, found across 140 different families, [...]
Quantum Algorithms and the Future of Precision Medicine
Precision medicine is reshaping healthcare by tailoring treatments to individual patients based on their unique genetic, environmental, and lifestyle factors. At the forefront of this revolution, the integration of quantum computing and machine learning [...]
Scientists Have Discovered a Simple Supplement That Causes Prostate Cancer Cells To Self-Destruct
Menadione, a vitamin K precursor, shows promise in slowing prostate cancer in mice by disrupting cancer cell survival processes, with potential applications for human treatment and myotubular myopathy therapy. Prostate cancer is a quiet [...]
Scientists reveal structural link for initiation of protein synthesis in bacteria
Within a cell, DNA carries the genetic code for building proteins. To build proteins, the cell makes a copy of DNA, called mRNA. Then, another molecule called a ribosome reads the mRNA, translating it [...]
Vaping Isn’t Safe: Scientists Uncover Alarming Vascular Risks
Smoking and vaping impair vascular function, even without nicotine, with the most significant effects seen in nicotine-containing e-cigarettes. Researchers recommend avoiding both for better health. Researchers have discovered immediate impacts of cigarette and e-cigarette [...]
Twice-Yearly Lenacapavir for PrEP Reduces HIV Infections by 96%
Twice-yearly injections of the capsid inhibitor drug lenacapavir can prevent the vast majority of HIV infections, according to a Phase 3 clinical trial published Wednesday in the New England Journal of Medicine. HIV pre-exposure [...]
Did Social Distancing Begin 6,000 Years Ago? Neolithic Villagers May Have Invented It
Social distancing may have roots 6,000 years ago, as research shows Neolithic villages like Nebelivka used clustered layouts to control disease spread. The phrase “social distancing” became widely recognized in recent years as people [...]
Decoding Alzheimer’s: The Arctic Mutation’s Role in Unusual Brain Structures
Researchers have uncovered how certain genetic mutations lead to unique spherical amyloid plaques in inherited forms of Alzheimer’s, offering insights that could advance our understanding of the disease and improve therapeutic strategies. An international collaboration [...]
How Your “Lizard Brain” Fuels Overthinking and Social Anxiety
New research by Northwestern Medicine reveals how humans have evolved advanced brain regions to interpret others’ thoughts, connecting these areas with the amygdala, a part of the brain involved in emotional processing. Study sought [...]
How Did Life Begin? Researchers Discover Game-Changing Clue
New research offers a potential explanation for the formation of early Earth protocells. Few questions have captivated humankind more than the mystery of life’s origins on Earth. How did the first living cells emerge? [...]
