Modulation of the Specificity of Carbapenems and Diazabicyclooctanes for Selective Activity against Mycobacterium tuberculosis
2022; American Society for Microbiology; Volume: 66; Issue: 9 Linguagem: Inglês
10.1128/aac.02357-21
ISSN1098-6596
AutoresJean‐Philippe Barnier, Saidbakhrom Saidjalolov, Flavie Bouchet, Louis Mayer, Zainab Edoo, Inès Sayah, Laura Iannazzo, Mélanie Ethève‐Quelquejeu, Jean‐Luc Mainardi, Emmanuelle Braud, Michel Arthur,
Tópico(s)Antibiotics Pharmacokinetics and Efficacy
ResumoTreatment 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.
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