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Scientific result | Antibiotics | Structural biology

Antibiotics are putting up a resistance

A team from the IBS has shown how some antibiotics become insensitive to the principal mechanisms of bacterial resistance.
Published on 17 January 2018

The DRF is increasing its research into the issue of antibiotic resistance, as made necessary by this major public health problem. While the Institut Frédéric-Joliot has recently developed a rapid screening test for antibiotic resistance, other researchers, notably at the IBS, are conducting research more upstream of this issue, as shown by this result involving radical-based chemistry as well as other strategies (in French: Du nouveau dans la stratégie antibiotique, and Révélation sur les phages, alternatives aux antibiotiques).

The biosynthesis pathways of many natural products are an important source of inspiration for the development of new, more efficient and environmentally friendly chemical synthesis processes. In this regard, radical-based chemistry allows difficult reactions in aqueous media, by involving high-energy intermediates. The 'radical SAM' family of proteins is capable of controlling these intermediates for regio- and stereo-specific reactions. The crystalline structure of the AprD4 protein, demonstrated by the IBS in collaboration with the University of Fudan (China), exceptionally reveals that the three-dimensional organization of the active site allows the substrate to adopt different conformations in order to eliminate a water molecule from a specific position (all while retaining the recognition specificity).

This modification allows certain antibiotics in the aminoglycoside family, used against animal bacterial diseases, to become insensitive to the principal bacterial resistance mechanisms.

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