Researchers discover new insights for antibiotic drug development

In two articles published in the current online issue of Nature Chemical Biology, researchers describe an approach that is more efficient in developing new antibiotics, those needed to kill the increasing number of infections resistant to multiple drugs.

“We’re striving to create new drugs that can have a positive impact on the growing threat of infectious diseases,” said Robert Fecik, an assistant professor of Medicinal Chemistry at the University of Minnesota College of Pharmacy and one of the lead authors of the study. “This type of research can help us make new antibiotic molecules.”

Officials at the Centers for Disease Control and Prevention have called antibiotic resistance one of the world’s most pressing public health problems. Once only found in hospitals, these “superbugs” are now being found in community settings, including schools, nursing homes, and locker rooms.

These infections don’t respond to common antibiotics such as erythromycin, which belong to a ring-shaped class of antibiotics called macrolides. Nearly all antibiotics in use today are natural molecules made by bacteria to kill their enemies. The bacteria use specialized proteins called enzymes to carry out the chemical steps in making these ring-shaped antibiotic molecules.

One way to increase the number of antibiotics for fighting infections is to start where nature stopped and engineer the enzymes to produce new molecules, and thus new antibiotics. But to do this more effectively, scientists need a clearer picture of how the enzyme molecules act upon the precursor to the antibiotic.

The Michigan team is the first to crystallize an enzyme in the process of closing the antibiotic ring, which illustrates exactly how the ring is formed. It is hoped that heir work will create important opportunities for drug discovery to stay one step ahead of the superbugs.