Seeing antibiotics in action inside a pathogenic bacterium

Every living cell relies on proteins in order to function and the process of protein synthesis — translation — is critical for survival. Bacteria are no exception, with molecular machines involved in translation being one of the most common targets for antibiotics.

Now, for the first time, scientists led by Julia Mahamid’s group at EMBL Heidelberg have visualised at atomic detail how antibiotics affect the process of protein production inside bacterial cells. This study, published in Nature, also marks the first time when scientists have observed atomic-level structural changes in the active translation machinery directly inside a cell, rather than using isolated molecules in a test tube. Importantly, this approach allowed them to identify mechanisms that such machines use to “talk” to each other inside cells.

The study was carried out in collaboration with researchers from the Max-Planck-Institute for Biophysical Chemistry, Göttingen, the Wellcome Centre for Cell Biology, University of Edinburgh, and Technische Universität Berlin. The research also involved contributions from the Zimmermann-Kogadeeva and Bork groups at EMBL Heidelberg, who helped the researchers carry out bioinformatics analyses to observe what diversity in ribosomal proteins looks like across >4000 representative bacteria.

Minuscule bacteria and molecular machines

Mahamid and her team are experts in studying the bacterium Mycoplasma pneumoniae using a technique called cryo-electron tomography (cryo-ET). This tiny bacterium, which causes atypical pneumonia in humans, has a fully-functional protein synthesis machinery, despite being only about ten-thousandth of a millimetre in size.

“We chose Mycoplasma for our studies because they are among the smallest and most minimal living cells, and have been widely used as model cells in systems biology and synthetic biology studies,” said Liang Xue, postdoc in the Mahamid group and the first author of the study.

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