Structural Basis for Linezolid Binding Site Rearrangement in the Staphylococcus aureus Ribosome

What is it about?

This study describes the molecular mechanism by which the potentially deadly superbug ‘Golden Staph’ evades antibiotic treatment, providing the first important clues on how to counter superbug antibiotic resistance. We have identified the first important clues on how to 'retool' antibiotics to counter the strategies bacteria enlist to evade the life-saving drugs. Using the latest generation electron microscopes at the Monash Ramaciotti Centre for Cryo-Electron Microscopy to image at the molecular level – for the first time – the changes that take place in superbugs that have become resistant to the most modern antibiotics. Examining bacterial samples of antibiotic-resistant Staphylococcus aureus or ‘Golden Staph’ taken from a hospital patient, they compared data of a non-resistant strain with their counterparts overseas. These included Shashi Bhushan from NTU, and Zohar Eyaland Nobel Laureate, Professor Ada Yonath from the Weizmann Institute who won the Nobel Prize for Chemistry in 2009. Using the combined data we could rationalise how the bacteria escapes drug treatment by a really important hospital antibiotic and describe in molecular detail how it becomes like a superbug. The bacteria mutates or evolves to change the shape of the molecule to which the antibiotic would bind so the drug can no longer fit there.

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Why is it important?

Understanding what changes have occurred in the bacterial molecule that has led it to b e drug resistant, is an important first step to the next phase of new drug design. The technique we have development is also critically important to be adopted by others to help speed up the arms race of antibiotic development.