Targeted modifications of neomycin and paromomycin: Towards resistance-free antibiotics?

Despite their clinical importance, saving numerous human lifes, over- and mis-uses of antibiotics have created a strong selective pressure on bacteria, which induces the emergence of (multi)resistant strains. Antibioresistance is becoming so pregnant that since 2017, WHO lists bacteria threatening most human health (AWaRe, ESKAPE lists), and those for which new antibiotics are urgently needed. Since the century turn, this context is leading to a burst in the chemical synthesis of new antibiotics, mostly derived from natural antibiotics. Among them, aminoglycosides, and especially the neomycin family, exhibit broad spectrum of activity and remain clinically useful drugs. Therefore, numerous endeavours have been undertaken to modify aminoglycosides with the aim of overcoming bacterial resistances.