Scientists Discover Molecule That Can Fight Drug-Resistant Bacteria

Drug resistance has become a hot topic over the last couple of years, and it’s bound to stay that way thanks to a rise in monkeypox and polio cases across the US. This pesky (and sometimes deadly) phenomenon occurs when bacteria, fungi, and other germs become impervious to medication, or even capable of destroying the medication once it’s entered the body. One such bacteria, called Gram-negative bacteria, is responsible for a range of health complications including urinary tract infections (UTIs), lung infections, gastroenteritis, and meningitis.

Gram-negative bacteria owes its resilience to a tough outer cell wall that prevents antibiotics and other treatments from permeating its walls. It also contains a number of efflux pumps, a mechanism by which the bacteria can flush unwanted molecules out of the cell. Together, the cell wall and efflux pumps often render antibiotics ineffective, making uncomfortable and life-threatening health issues difficult to treat. But fabimycin, a newly synthesized compound, appears to permeate Gram-negative bacteria’s defenses enough to let medical treatments do their job.

Fabimycin works by targeting an enzyme called FabI, which is integral to the success of Gram-negative bacteria’s defense mechanisms. While FabI inhibitors have been used to treat staph infections (Staphylococcus aureus), scientists haven’t been able to synthesize one capable of bypassing Gram-negative bacteria’s cell walls—until now. According to new research published in ACS Central Science, a team of chemists and molecular biologists at the University of Illinois at Urbana-Champaign, the Broad Institute of MIT and Harvard, and the Walter Reed Army Institute of Research successfully created fabimycin while working to treat a slew of drug-resistant diseases.

So far, tests have shown that fabimycin is an effective tool in treating over 200 isolated Gram-negative bacterial diseases, including E. coli, a rare case of pneumonia called Klebsiella pneumoniae, and a lung and blood pathogen called Acinetobacter baumannii. Lab-simulated treatments, however, are only as effective as their real-world counterparts. In mice, fabimycin not only helped permeate Gram-negative bacteria but also reduced the concentration of those bacteria to the animals’ pre-infection levels.

The discovery of this powerful compound gives the researchers hope that antibiotics might someday be altered to more effectively target drug-resistant diseases. “Fabimycin has translational promise, and its discovery provides additional evidence that antibiotics can be systematically modified to accumulate in Gram-negative bacteria and kill these problematic pathogens,” the team said.

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