This study demonstrated how nuclear magnetic resonance (NMR) proves to be a powerful analytical tool for better tracking the fate of antibiotics in the face of resistance phenomena and potentially helping to make them more effective.
The production of enzymes called β-lactamases is one of the main clinical indicators of the emergence of resistance in many bacteria. These β-lactamases have the capacity to degrade β-lactam antibiotics*, rendering them inactive. Produced by the bacterium in its periplasm, a compartment delimited by its inner and outer membranes, these enzymes reinforce the bacterium’s defense against antibiotic intrusion. Thanks to the development of a method for in situ nuclear magnetic resonance monitoring of the enzymatic activity taking place in the cell, it has been possible to analyze in real time the degradation of β-lactams by β-lactamases in resistant strains. Using specific β-lactamase enzyme inhibitors, the ability of β-lactams to cross the outer membrane, interact with their target and ultimately block at least partial antibiotic degradation has been assessed. These measurements provide information on the nature and location of these inhibitor-enzyme interactions, by measuring them directly within the cell.
This study, published in J. Am. Chem. Soc., shows that NMR on living cells constitutes a powerful analytical tool for studying new molecules specifically targeting the molecular components of the bacterial periplasm responsible for antibiotic resistance. This approach will make it possible to assess the efficacy of drugs directly in their environment, opening the way to personalized medicine by proposing a specific antibiotic treatment for each patient according to the micro-organism responsible for the resistant infection.
Collaborations : M. Arthur (INSERM, Paris), A. Dessen (IBS, Grenoble)