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. 2022 Sep 20;66(9):e0235721.
doi: 10.1128/aac.02357-21. Epub 2022 Aug 9.

Modulation of the Specificity of Carbapenems and Diazabicyclooctanes for Selective Activity against Mycobacterium tuberculosis

Jean-Philippe Barnier  1   2   3 , Saidbakhrom Saidjalolov  4 , Flavie Bouchet  4 , Louis Mayer  1 , Zainab Edoo  1 , Inès Sayah  1 , Laura Iannazzo  4 , Mélanie Ethève-Quelquejeu  4 , Jean-Luc Mainardi  1   2   3 , Emmanuelle Braud  4 , Michel Arthur  1
Affiliations

Modulation of the Specificity of Carbapenems and Diazabicyclooctanes for Selective Activity against Mycobacterium tuberculosis

Jean-Philippe Barnier et al. Antimicrob Agents Chemother. .

Abstract

Treatment of multidrug-resistant tuberculosis with combinations of carbapenems and β-lactamase inhibitors carries risks for dysbiosis and for the development of resistances in the intestinal microbiota. Using Escherichia coli producing carbapenemase KPC-2 as a model, we show that carbapenems can be modified to obtain drugs that are inactive against E. coli but retain antitubercular activity. Furthermore, functionalization of the diazabicyclooctanes scaffold provided drugs that did not effectively inactivate KPC-2 but retained activity against Mycobacterium tuberculosis targets.

Keywords: Mycobacterium tuberculosis; carbapenem; carbapenemase; diazabicyclooctane; narrow-spectrum drug.

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Conflict of interest statement

The authors declare no conflict of interest.

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