Harvard Researchers Develop New Antibiotic to Overcome Antimicrobial Resistance
In a groundbreaking development, a team of researchers from Harvard University has created a new antibiotic that has the potential to overcome antimicrobial resistance mechanisms. This breakthrough comes at a crucial time when many modern drugs have become ineffective, leading to a global public health crisis. Led by Andrew Myers, the Amory Houghton Professor of Chemistry and Chemical Biology, the team reports that their synthetic compound, cresomycin, has shown the ability to kill drug-resistant bacteria strains, including Staphylococcus aureus and Pseudomonas aeruginosa.
The researchers have discovered that cresomycin demonstrates an improved ability to bind to bacterial ribosomes, which are biomolecular machines responsible for controlling protein synthesis. Disrupting ribosomal function is a common approach used by existing antibiotics, but some bacteria have developed shielding mechanisms that render these drugs ineffective. However, cresomycin has proven to be effective against these shielded bacteria.
While the safety and effectiveness of cresomycin in humans are yet to be determined, the results of the study show promising inhibitory activity against a wide range of pathogenic bacterial strains. These strains are responsible for causing the deaths of over a million people every year. Compared to clinically approved antibiotics, cresomycin and similar drugs have shown significantly improved efficacy.
Cresomycin is just one of several compounds developed by Myers’ team with the goal of combating superbugs. The researchers will continue to advance these compounds through preclinical profiling studies, thanks to a $1.2 million grant from the Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator (CARB-X). CARB-X is a global nonprofit partnership based at Boston University that supports early-stage antibacterial research and development.
The inspiration for cresomycin comes from lincosamides, a class of antibiotics that includes the commonly prescribed drug clindamycin. However, unlike clindamycin, cresomycin is fully synthetic and features chemical modifications that cannot be achieved through existing means. By leveraging the power of organic synthesis, the researchers have been able to design new antibiotics with almost limitless possibilities.
One of the challenges in developing antibiotics is that bacteria can develop resistance to drugs that target ribosomes by expressing genes that produce enzymes called ribosomal RNA methyltransferases. These enzymes prevent the drug components from binding to and disrupting the ribosome, rendering the drug ineffective. To overcome this problem, Myers and his team engineered cresomycin into a rigidified shape that closely resembles its binding target, giving it a stronger grip on the ribosome. This unique feature allows cresomycin to bypass the shielding mechanisms of bacteria.
The researchers used a method called component-based synthesis to arrive at cresomycin. This method involves building large molecular components of equal complexity and bringing them together at late stages, similar to pre-building sections of a complicated LEGO set before assembling them. This modular and completely synthetic system enables the researchers to create and test hundreds of target molecules, greatly speeding up the drug discovery process.
The importance of developing new antibiotics cannot be overstated. Antibiotics are the foundation of modern medicine, enabling cutting-edge medical procedures such as surgeries, cancer treatments, and organ transplants. Without effective antibiotics, these life-saving procedures would be impossible.
Myers’ research received early support from Harvard’s Blavatnik Biomedical Accelerator, which awarded funding to his lab in 2013 for testing drug compounds. The Office of Technology Development protected the innovations of the Myers Research Group and, along with the Blavatnik Biomedical Accelerator, will continue to support the research team throughout the CARB-X agreement. The newly awarded CARB-X funding will allow the researchers to further optimize and profile their drug leads.
Funding and support from organizations like the Blavatnik Biomedical Accelerator and CARB-X are crucial for the discovery and development of new antibiotics. The innovations from the Myers Research Group have the potential to address the global health need for effective antibiotics.
The research was supported by the National Institutes of Health and the National Science Foundation, highlighting the importance of collaboration and investment in scientific advancements that can save lives and combat antimicrobial resistance.
