Harvard scientists discover compound that kills antibiotic-resistant superbugs

By James Gamble via SWNS

A new synthetic compound discovered by scientists is "highly effective" at killing deadly superbugs resistant to antibiotics.

The compound, cresomycin, kills many strains of dangerous, drug-resistant bacteria including Staphylococcus aureus and Pseudomonas aeruginosa.

Though the new drug is yet to be tested on humans, researchers say it could be used to combat the deadly bacterial strains and save millions of lives.

Cresomycin is one of several promising compounds the team from Harvard University in the US has developed in their pursuit of developing drugs to win the war against superbugs.

The Harvard team found that their new molecule demonstrates an improved ability to bind to bacterial ribosomes - biomolecular machines that control protein synthesis.

The team, led by Dr. Andrew Myers, was recently awarded $1.2M (£956,000) by a nonprofit organization to develop oral antibiotics that kill drug-resistant infections.

Disrupting ribosomal function is a hallmark of many existing antibiotics, though some superbug bacteria have evolved shielding mechanisms that prevent drugs from working.

The new molecule draws inspiration from the chemical structures of 'lincosamides' - a class of antibiotics that includes the commonly prescribed clindamycin.

Like many antibiotics, clindamycin is made via semisynthesis - a process in which complex products isolated from nature are modified directly for drug applications.

The new Harvard compound, however, is fully synthetic and features chemical modifications that cannot be accessed through existing means.

Study co-author Ben Tresco said: "The bacterial ribosome is nature’s preferred target for antibacterial agents, and these agents are the source of inspiration for our program.

“By leveraging the power of organic synthesis, we are limited almost only by our imagination when designing new antibiotics.”

Bacteria can develop resistance to antibiotic drugs by expressing genes that produce enzymes called ribosomal RNA methyltransferases.

The enzymes box out the drug components that are designed to latch onto and disrupt the ribosome, ultimately blocking the drug’s activity.

To solve the problem, Dr. Myers and his team engineered their compound into a rigid shape that closely resembles its target - giving it a far stronger grip on the ribosome.

The researchers describe their drug as being 'pre-organized' for ribosomal binding as it doesn’t need to expend as much energy conforming to its target as existing drugs.

The team identified cresomycin using component-based synthesis, a method pioneered by Dr Myers' lab that involves building large molecular components of equal complexity and bringing them together at late stages - likened to pre-building sections of a complicated LEGO set before assembling them.

This modular, completely synthetic system allows them to make and test not just one but hundreds of target molecules, which greatly speeds up the drug discovery process.

Dr. Myers said: “While we don’t yet know whether cresomycin and drugs like it are safe and effective in humans, our results show significantly improved inhibitory activity against a long list of pathogenic bacterial strains that kill more than a million people every year, compared with clinically approved antibiotics."

Co-author Kelvin Wu added: “Antibiotics form the foundation on which modern medicine is built.

“Without antibiotics, many cutting-edge medical procedures like surgeries, cancer treatments, and organ transplants, cannot be done.”

Dr. Myers’ study, published in the journal Science, received early support from Harvard’s Blavatnik Biomedical Accelerator, which awarded funding to his lab in 2013 to enable testing of drug compounds.