September 29, 2022 -- EMBL Heidelberg researchers, led by group leader and senior scientist Julia Mahamid, PhD, have visualized at atomic detail how antibiotics affect the process of protein production inside bacterial cells.
In their study, published September 28 in the journal Nature, the researchers observed atomic-level structural changes in the active translation machinery directly inside a cell, rather than using isolated molecules in a test tube. This approach allowed them to identify mechanisms that such machines use to "talk" to each other inside cells.
Mahamid and her team are experts in studying the bacterium Mycoplasma pneumoniae using cryo-electron tomography (cryo-ET). Cryo-ET allows researchers to take serial images of flash-frozen biological samples using an electron microscope and combine the resulting images to form a three-dimensional view of a cell.
Ribosomes are one of the most prominent structures visible in the cryo-ET image of the Mycoplasma cell. This method allowed researchers to not only spot and count the ribosomes inside the bacteria, but also see their structure in atomic resolution. In addition, using the cryo-ET the researchers could observe what happens when antibiotics enter the cell and bind to ribosomes.
The researchers observed that the interactions between ribosomes and other complexes in the cell changed in response to the drug, suggesting that an antibiotic can have an effect that reaches far beyond the specific complex it binds to.
"On the one hand, this can help understand off-target effects of antibiotics and may also help design combinations of antibiotics to increase their efficiency," said Mahamid.
The EMBL team collaborated with researchers from the Max-Planck-Institute for Biophysical Chemistry, Göttingen, the Wellcome Centre for Cell Biology, the University of Edinburgh, and Technische Universität Berlin, with contributions from Zimmermann-Kogadeeva and Bork groups at EMBL Heidelberg.