The misuse of antibiotics contributes to the growing problem of antibiotic resistance. Antibiotics are often prescribed unnecessarily or overprescribed, leading to increased resistant bacteria. In some countries, antibiotics can be purchased over the counter without a prescription, making it easier for people to use them inappropriately and contributing to developing drug-resistant infections. Additionally, antibiotics may not be used correctly—taking too little or stopping treatment early can lead to incompletely treated infections that may result in mutated, more resistant pathogens than their predecessors.
Professor John E. Moses of Cold Spring Harbor Laboratory (CSHL) reasoned that if a molecule could be designed to respond similarly, it might also be able to find and attack bacteria quickly. In his lab, he created an antibiotic compound with atoms arranged so that when exposed to certain conditions, it could rearrange its chemical structure and become more effective against superbugs. He found that this shape-shifting was successful in killing drug-resistant E. coli as well as other resistant strains of bacteria. This new weapon can potentially revolutionize the fight against these dangerous pathogens.
Moses found that by using bullvalene as the base for a new type of lubricant, he could create a substance that changed shape in response to external conditions. It could adapt to different environments, like extreme temperatures or pressure. It also had superior anti-friction properties compared to previous lubricants. With his discovery, Moses created a new class of materials: molecularly fluid substances known today as synthetic lubricants. These revolutionary molecules drastically improved efficiency and productivity across many industries—transport and manufacturing to aerospace technology. They helped reduce friction costs, saving time and money while promoting energy conservation efforts worldwide.
The new antibiotic successfully combats vancomycin-resistant bacteria and other drugs, such as ampicillin. Moses hopes his combination therapy will become a standard treatment for many bacterial infections. “This provides a platform technology which can be used for multiple drug-resistant organisms,” he says. It could be applied to viruses with similar characteristics; however, more research is needed before conclusions can be drawn from this early work.
The next step in Moses’s research is to replicate the results with different types of bacteria and in larger animals. The team then plans to scale up production and start clinical trials so that one day, a shape-shifting antibiotic may be available for patients fighting life-threatening infections. Such an accomplishment would mark a huge step forward in our quest to outsmart drug-resistant bacteria — making us all safer from these insidious little bugs.
Vancomycin is one of the most important antibiotics in clinical use, but it has been increasingly used against multidrug-resistant bacteria. This has led to an urgent need for novel therapies to combat these infections. In this study, Ottonello et al. present a new approach for vancomycin-based antibiotic therapy by using shapeshifting bullvalene-linked dimers as effective antibacterial agents. Bullvalene is a small molecule that can self-assemble into two different shapes depending on its environment and temperature; thus, the linker between vancomycin molecules provides enhanced antibacterial activity without altering their core structure or mechanism of action.
The authors found that the dimer was more effective than either monomer alone at inhibiting the growth of antibiotic-resistant gram-positive bacteria with minimal cytotoxicity in vitro and improved efficacy in vivo compared to vancomycin alone. These findings provide an exciting opportunity to develop novel antibiotics based on this promising scaffold system. They could have tremendous implications for treating difficult infectious diseases caused by multidrug-resistant bacteria.