Reseachers discover new insights for antibiotic drug development

Sep 11, 2006

University of Minnesota and University of Michigan researchers have discovered a new method of developing antibiotics, an important step in fighting the growing number of drug-resistant infections.

In two articles published in the current online issue of Nature Chemical Biology, researchers describe an approach that is more efficient--and environmentally friendly--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," says Robert Fecik, Ph.D., 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 interdisciplinary team of scientists, including research professors David H. Sherman and Janet L. Smith from the University of Michigan's Life Sciences Institute and Fecik of University of Minnesota College of Pharmacy, is the first to crystallize an enzyme in the process of closing the antibiotic ring, which illustrates exactly how the ring is formed.

Their work creates important opportunities for drug discovery to stay one step ahead of the superbugs.

"Having the tools to make the next generation of macrolide antibiotics is crucial because these drugs are so well tolerated and have so few side effects," Smith said. "They are really a great class of antibiotics, so we need more of them."

These macrolide antibiotics are of particular interest because bacteria make them in a way that potentially allows for thousands of slightly different compounds to be synthesized and tested for antibiotic activity.

The structure of macrolides is a large ring, itself constructed from a linear molecule, which is built in an assembly-line fashion from smaller molecules. An enzyme at the end of the chain triggers the ring formation that results in antibiotic formation.

"These findings are likely to enable the development of powerful new methods to build structural diversity into large ring systems that are a key component of many types of macrolide antibiotic molecules. This will provide yet another strategy to stay ahead of the emerging and persistent antibiotic resistance threat," Sherman said.

In traditional drug development, researchers start with an existing antibiotic and chemically manipulate it to develop a new version of the original drug. With the new approach outlined in the article, researchers describe a method that can be used to get the bacteria itself to produce new compounds that turn into the ring structure and may be useful as new drugs.

Typical drug development involves chemical manipulations that result in chemical waste, which can be difficult to dispose of and is hazardous to the environment.

This research implies it is realistic to develop a more environmentally friendly way to discover more potential drug compounds with less chemical manipulation, and thus less chemical waste.

Source: University of Minnesota

Explore further: Study finds codeine often prescribed to children, despite available alternatives

add to favorites email to friend print save as pdf

Related Stories

Synthetic gene circuits pump up cell signals

Apr 08, 2014

(Phys.org) —Synthetic genetic circuitry created by researchers at Rice University is helping them see, for the first time, how to regulate cell mechanisms that degrade the misfolded proteins implicated ...

New light shed on key bacterial immune system

Apr 07, 2014

New insights into a surprisingly flexible immune system present in bacteria for combating viruses and other foreign DNA invaders have been revealed by researchers from New Zealand's University of Otago and ...

Recommended for you

AMA examines economic impact of physicians

13 hours ago

(HealthDay)—Physicians who mainly engage in patient care contribute a total of $1.6 trillion in economic output, according to the American Medical Association (AMA)'s Economic Impact Study.

Less-schooled whites lose longevity, study finds

13 hours ago

Barbara Gentry slowly shifts her heavy frame out of a chair and uses a walker to move the dozen feet to a chair not far from the pool table at the Buford Senior Center. Her hair is white and a cough sometimes interrupts her ...

How to keep your fitness goals on track

14 hours ago

(HealthDay)—The New Year's resolutions many made to get fit have stalled by now. And one expert thinks that's because many people set their goals too high.

Low tolerance for pain? The reason may be in your genes

14 hours ago

Researchers may have identified key genes linked to why some people have a higher tolerance for pain than others, according to a study released today that will be presented at the American Academy of Neurology's 66th Annual ...

User comments : 0

More news stories

Cancer stem cells linked to drug resistance

Most drugs used to treat lung, breast and pancreatic cancers also promote drug-resistance and ultimately spur tumor growth. Researchers at the University of California, San Diego School of Medicine have discovered ...

Finnish inventor rethinks design of the axe

(Phys.org) —Finnish inventor Heikki Kärnä is the man behind the Vipukirves Leveraxe, which is a precision tool for splitting firewood. He designed the tool to make the job easier and more efficient, with ...

Making graphene in your kitchen

Graphene has been touted as a wonder material—the world's thinnest substance, but super-strong. Now scientists say it is so easy to make you could produce some in your kitchen.