Résumé
According to the World Health Organization (WHO), antimicrobial resistance is a serious global health issue. Overcoming antibiotic resistance involves several strategies, including the inhibition of resistance mechanisms. Among the various resistance mechanisms, aminoglycoside phosphotransferases, APHs, catalyze the transfer of the γ-phosphate from a nucleotide donor to various aminoglycosides, leading to their inactivation. In this work, using a fragment-based drug design (FBDD) approach, we have identified and characterized a promising APH inhibitor capable of increasing the sensitivity of bacteria resistant to aminoglycosides. It is therefore a good candidate for the future development of APH inhibitors to be prescribed in combination with aminoglycosides. This molecule is a competitive inhibitor of ATP, the phosphate donor of APHs. Further studies are required to optimize this molecule to improve its specificity for APHs and its bioavailability in bacteria.