Studies show that single water molecules may be resistant to antibiotics

New high-resolution structures of the bacterial ribosome have been tested by researchers at the University of Illinois at Chicago showing that one water molecule may be to blame -; and possible solution -; against antibiotics.

The findings of a new UIC study are published in the journal Nature Chemical Biology.

Pathogenic bacteria become resistant to antibiotics when they develop the ability to defeat the drugs designed to kill them. Every year in the U.S., millions of people suffer from antibiotic-resistant infections, and thousands of people die as a result.

The development of new drugs is a key way in which the scientific community is trying to reduce its antibiotic resistance.

The first thing we need to do to make improved drugs is to gain a better understanding of how antibiotics work and how ‘bad bacteria’ resist them.. “

Alexander Mankin, Research Co-author and Professor of Pharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago

Mankin and his colleague Yury Polikanov, an associate professor of biological sciences at UIC’s Liberal College of Arts and Sciences, have been studying the action mechanism of one of the most popular types of antibiotics being used. ‘practice in the clinic today -; macrolides.

“Macrolides are among the most successful antibiotics commonly used for the treatment of communicable diseases in the community – people receive macrolide antibiotics, such as azithromycin, for example, all the time,” he said. Polikanov, corresponding author of the paper. “Macrolides work by entering bacteria and binding to the ribosomes, the cell’s protein synthesis engine. As soon as they bind, the drug prevents ribosomes from making new proteins, thus stopping bacteria from growing and reproducing. However, immune bacteria modify the ribosomes so that a drug can no longer bind to them. “

Through years of partnership between their two laboratories, UIC researchers were able to understand how macrolides bind to the ribosome, how bacteria react with macrolides and how they grow against of these common drugs. They also learned how to capture high-resolution images of the ribosomes attacked by antibiotics.

“We compared the hi-res structures of the ribosomes from sensitive and immune bacteria and found that water molecules required for tight binding of antibiotics were not present in the ribosomes from the drug-resistant lice. the ribosomes from the drug- resistant to bacteria, there was no room for this water molecule, “said Polikanov.

The water molecule, the researchers found, acts as a bridge between the ribosome and an antibiotic. When immune bacteria alter the chemical shape of their ribosomes, this bridge between the ribosome and the drug cannot be built.

Although the scientific community has long estimated that differences in the structures of sensitive and resistant ribosomes were important -; why these changes were not previously known.

“This study offers the first definitive explanation of why macrolides cannot bind to the ribosomes of immune bacteria,” Mankin said.

“We are very pleased with this discovery,” said Polikanov. “Because we now know exactly what macrolide antibiotics interact with their target, the ribosome. This finding is important because it will inform and assist the development of new antibiotics that do not require this molecule of water to bind. There is a huge demand for such drugs. which is able to kill even those bacteria that have grown up against the drugs currently in use. “