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Communicating science: Andrei Korostelev using structural biology to tackle antibiotic resistance

Andrei Korostelev, PhD, professor of RNA therapeutics, studies how bacteria can develop resistance to antibiotics, which has become a problem in treating infection.

“Antibiotic resistance may cause the next global health crisis,” Dr. Korostelev said. “We know that some bacteria have already become resistant to every widely used antibiotic.”

He noted that a recent survey of health care professionals showed nearly 60 percent of participants encountered patients whose infections didn’t respond to any antibiotic. This research shows the arsenal of effective antibiotics is depleted and needs to be replenished, which will require studying how the infection grows, how antibiotics help kill bacteria and how bacteria become resistant.

“An antibiotic is like a wrench thrown into the works of an assembly line jamming a step in production,” Korostelev said. “Most antibiotics block one of the central assembly lines that all bacteria depend on to reproduce their genetic code and grow.”

Korostelev’s lab in the RNA Therapeutics Institute at UMass Chan Medical School studies ribosomes, which are the cellular machines that make proteins. The ribosomes work nonstop to make proteins so the bacteria can grow and divide. His lab works to understand how the ribosomes read the genetic code stored in RNA and how they build proteins. The major technology for these studies is cryo-EM, which is available at the Medical School.

“Thanks to work done in many labs, we now know the atomic structure of the ribosome. We also know where the antibiotics—which are thousands of times smaller than the ribosome—bind and jam this large molecular machine,” he said.

This knowledge has already been used to make new and better antibiotics that can help fight some antibiotic-resistant infections. But Korostelev said there is more research to be done. Bacteria can sense the jammed ribosomes and slow their growth, which gives them time to develop antibiotic resistance.

“We need to learn more about the biology of bacterial cells, so we can expand the arsenal of effective antibiotics to be better prepared to fight future antibiotic-resistant infections,” he said.

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