:
Aminoglycosides and β-lactams are the most commonly used antimicrobial agents in clinical
practice. This occurs because they are capable of acting in the treatment of acute bacterial infections.
However, the effectiveness of antibiotics has been constantly threatened due to bacterial pathogens
producing resistance enzymes. Among them, the aminoglycoside-modifying enzymes (AMEs)
and β-lactamase enzymes are the most frequently reported resistance mechanisms. AMEs can inactivate
aminoglycosides by adding specific chemical molecules in the compound, whereas β-lactamases
hydrolyze the β-lactams ring, preventing drug-target interaction. Thus, these enzymes provide a scenario
of multidrug-resistance and a significant threat to public health at a global level. In response to
this challenge, in recent decades, several studies have focused on the development of inhibitors that
can restore aminoglycosides and β-lactams activity. In this context, peptides appear as a promising
approach in the field of inhibitors for future antibacterial therapies, as multiresistant bacteria may be
susceptible to these molecules. Therefore, this review focused on the most recent findings related to
peptide-based inhibitors that act on AMEs and β-lactamases, and how these molecules could be used
for future treatment strategies.
