Antibiotics, while life-saving, can also wreak havoc on healthy systems. The drugs work by attacking the protein-synthesizing center (ribosomes) in bacteria. When the ribosomes in human cells are mistaken for bacterial ribosomes, antibiotics can cause a range of side effects from nausea to kidney failure. To understand what conditions cause healthy cells to be attacked, scientists are implementing novel imagining techniques to study interactions between ribosomes and drugs. Researchers have shown that slight modifications to the binding sites between the drug and ribosomes are effective in reducing the side effects without diminishing the efficacy of antibiotics. However, it is difficult to alter the sites effectively without physically being able to see the changes.
Previously, imaging techniques could only capture the binding process when everything was frozen. This does not provide an accurate picture; just like flowers in the jungle can’t grow in the arctic, some cellular processes don’t happen at low temperatures. At Stanford’s Linac Coherent Light Source (LCLS), high-energy x-rays are shot at the ribosomes, bounce off ribosomes binding with antibodies, and then scatter off into the detector, much like the flash on the camera. The x-rays in this technique, called x-ray crystallography, are very powerful and would destroy the ribosomes before the picture could be taken, if they weren’t frozen. To produce more accurate and informative snapshots, the antibodies and ribosomes were kept in room-temperature liquid and fed continuously into the x-ray stream using a thin tube. The samples are still destroyed as they are imaged, but the continuous feed of samples ensures that there are enough snapshots to tell the story of ribosome and antibody binding.
This breakthrough in imaging is invaluable. By visualizing the bonding processes, scientists can execute informed alterations to the drugs, reducing the chance of attacking a human cell. This method of imaging can facilitate production on antibiotics with particularly deadly strains and drug-resistant bacteria. Beyond antibiotics, the technique is a powerful probe to observing and thus understanding biological processes and human DNA.
Managing Correspondent: Cari Cesarotti
Press Article: https://www6.slac.stanford.edu/news/2018-08-06-catching-dance-antibiotics-and-ribosomes-room-temperature.aspx
Original Journal Article: Aminoglycoside ribosome interactions reveal novel conformational states at ambient temperature. Nucleic Acids Research.
Image: Greg Stewart/SLAC National Accelerator Laboratory