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Unravelling the Secret of Antibiotic Resistance

Proteins protect ribosomes from antibiotic attack, researchers find

Scientists at the University of Leeds in the United Kingdom have answered a 25-year-old question about how a family of proteins allows bacteria to resist the effects of certain antibiotics.

Proteins of the ABC-F family are a major source of antibiotic resistance in “superbugs,” such as Staphylococcus aureus, a group of bacteria that includes methicillin-resistance S. aureus (MRSA).

The new findings, published in the American Society for Microbiology journal mBio, provide the first direct evidence of how this family of proteins “protects” the bacterial ribosome—the protein makers in cells—from being blocked by antibiotics. Ordinarily, the ribosome is an ideal target for antibiotics because living bacteria cannot grow without it, but when bacteria produce ABC-F proteins, many antibiotics no longer work.

Until now, there has been a longstanding debate regarding the exact function of ABC-F proteins. Scientists have been divided in their support for two separate ideas: that the proteins are pumps that remove antibiotics from bacterial cells, or that they interact with the bacteria’s ribosomes to stop antibiotics from blocking them.

This kind of fundamental research provides a better picture of the molecular basis for antibiotic resistance, according to the researchers. It can offer valuable information that might be used in the future to design antibiotics to bypass antibiotic resistance, when scientists are able to understand more about the properties that allow drugs to enter bacterial cells.

Dr. Liam Sharkey, who conducted the research, said: “These findings provide the first direct evidence that these proteins directly protect the ribosome. As a result, the goal-posts of our research have changed; we can now zoom in and try to work out the exact details of how this protection is happening.

“Our results suggest that the proteins work by removing antibiotics when they bind their targeted ribosome. It’s a bit like the proteins are bouncers at a ribosome nightclub; the bouncer’s job is to keep kicking out antibiotics that are trying to get in and cause trouble.”

The debate about the ABC-F protein family wasn’t settled until now because of the technical challenges associated with the research and because much of the attention of academics in the field has been focused on the idea that the proteins work as pumps.

Source: Medical Xpress; March 22, 2016.

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