New antibiotic would make it more difficult for bacteria to develop drug resistance, UIC researchers say

Bacterial resistance may be nearly impossible thanks to a new antibiotic researched by scientists at the University of Illinois Chicago.

The antibiotic attacks bacteria in two different ways, making it 100 million times more difficult for that bacteria to develop resistance, researchers found in a new study published Monday.

Bacterial resistance, also called antibiotic resistance, happens when bacteria change so that antibiotics can't kill them or stop their growth. That can make it difficult, if not impossible, to treat a bacterial infection. The World Health Organization considers bacterial resistance a global public health threat.

UIC scientists examined how a class of synthetic antibiotic drugs called macrolones disrupt how bacteria function to fight infectious diseases. Their findings, published in Nature Chemical Biology, determined that macrolones can both interfere with protein production within the cells of the bacteria and corrupt its DNA structure.

Since the bacteria would have to fight both attacks at the same time, drug resistance would be nearly impossible, researchers found.

Two UIC laboratories were involved with the research. The labs are led by Yury Polikanov, associate professor of biological sciences; Alexander Mankin, professor of pharmaceutical sciences; and Nora Vázquez-Laslop, research professor of pharmacy.

Polikanov's team, which specializes in structural biology, studied how the antibiotic interacts with the ribosome, the vital part of the cell responsible for making protein. The antibiotic is able to strongly bind to the ribosome and block it. Other experiments found that the antibiotic can also target a specific enzyme in the bacteria called DNA gyrase.

"Ribosomes are absolutely essential, bacteria can't live without them. And it can't live with DNA gyrase," Polikanov said.

Attacking the ribosome and DNA gyrase are used separately in existing antibiotics, Polikanov explained. But what makes this drug special is it is able to simultaneously attack the bacteria in those two ways, which has not been done successfully before.

The drug was developed by scientists in China in partnership with the UIC researchers.

"Science transcends governments and country borders," Mankin said. "Governments might have their problems, but science operates on a different level. If it weren't for this collaboration, we would not have this. We would not have these compounds if it weren't for our Chinese partners, and they wouldn't have our findings."

The results are a long way from becoming drugs that doctors can prescribe to fight infections. Developing antibiotics takes years and lots of money, Mankin said.

"It's a constant race between bugs becoming resistant and companies developing new antibiotics," he said. "What our work has shown is there is a pathway to the clinical drug. ... Our hope is that someone, whether it's a company in China, in the U.S., or anywhere in the world, can take this finding and start making something that is clinically useful. We think our knowledge will accelerate that effort."

Polikanov and other UIC scientists also worked with researchers at Harvard to develop a different synthetic antibiotic that fights drug-resistant bacteria. They published their findings in February.