Health
Studies show that a single water molecule can cause antibiotic resistance
New high-resolution structures of bacterial ribosomes determined by researchers at the University of Illinois at Chicago indicate that a single water molecule may be the cause-; and possible solutions-; antibiotic resistance of.
The results of the new UIC study are published in the journal Nature Chemical Biology.
Pathogens become resistant to antibiotics as they develop their ability to defeat drugs designed to kill them. Every year in the United States, millions of people suffer from antibiotic-resistant infections, resulting in the death of thousands.
The development of new drugs is an important way the scientific community is trying to mitigate the effects of antibiotic resistance.
The first thing we need to do to make an improved drug is to better understand how antibiotics work and how “bad bugs” become resistant to them. is.. “
Alexander Mankin, Research Co-author, Professor, Faculty of Pharmaceutical Sciences, University of Illinois, Chicago
Mankin and his colleague, Yuri Polykanov, an associate professor of biological sciences at the UIC Liberal Arts and Sciences University, are studying the mechanism of action of the most popular types of antibiotics used in clinics today. I will. Macrolide.
“Macrolide antibiotics are one of the most successful antibiotics commonly used to treat community-acquired infections. Macrolide antibiotics, such as azithromycin, are always available.” Said Polykanov, the corresponding author of this treatise. “Macrolide antibiotics work by invading bacteria and binding to the ribosome, the cell’s protein synthesis machine. When bound, the drug prevents the ribosome from making new proteins, causing bacterial growth and replication. However, resistant bacteria alter the ribosomes and the drug can no longer bind to them. “
Through a long-standing partnership between the two laboratories, UIC researchers have learned how macrolides bind to the ribosome, how bacteria respond to macrolides, and these commonly used drugs. I was able to understand how to become resistant to. They also learned how to capture high-resolution images of antibiotic-invaded ribosomes.
“Comparing the high-resolution structures of susceptible and resistant ribosomes, we found that the water molecules required for tight binding of antibiotics were not present in drug-resistant ribosomes. -Resistant bacteria, there was no room for this water molecule, “said Polykanov.
The water molecules discovered by researchers act as a bridge between ribosomes and antibiotics. When resistant strains change the chemical composition of the ribosome, this bridge cannot be built between the ribosome and the drug.
The scientific community has long speculated that differences in the structure of sensitive and resistant ribosomes are important-; the reason these changes interfere with drug action was previously unknown.
“This study provides the first compelling explanation for why macrolide antibiotics cannot bind to the ribosomes of resistant strains,” Mankin said.
“We are very excited about this discovery,” Polykanov said. “Once we know how macrolide antibiotics interact exactly with the target ribosome, this discovery informs us in the development of new antibiotics that do not require this water molecule to bind. It’s important to promote. There is a great demand for such drugs. It can even kill bacteria that have become resistant to the drugs currently in use. “
Source:
Journal reference:
Svetrov, MS, et al.. (2021) The structure of the Erm-modified 70S ribosome reveals the mechanism of macrolide resistance. Nature Chemical Biology.. doi.org/10.1038/s41589-020-00715-0..
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