Aminoglycosidesand 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 aminoglycosidemodifying 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 βlactams 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.

中文翻译：

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开发抑制氨基糖苷修饰酶和β-内酰胺酶以控制耐药细菌的肽。

氨基糖苷类和β-内酰胺类是临床实践中最常用的抗菌剂。发生这种情况是因为它们能够治疗急性细菌感染。然而，由于细菌病原体产生抗性酶，抗生素的有效性一直受到威胁。其中，氨基糖苷修饰酶（AMEs）和β-内酰胺酶是最常报道的耐药机制。AME可以通过在化合物中添加特定的化学分子来使氨基糖苷失活，而β-内酰胺酶则水解β-内酰胺环，从而防止药物-靶标相互作用。因此，这些酶在全球范围内提供了多重耐药性和对公共卫生的重大威胁。为了应对这一挑战，最近几十年来，一些研究集中在可以恢复氨基糖苷和β-内酰胺活性的抑制剂的开发上。在这种情况下，由于多抗细菌可能对这些分子敏感，因此肽在抑制剂领域中有望成为未来抗菌疗法的一种有前途的方法。因此，本综述着重于与作用于AMEs和β-内酰胺酶的基于肽的抑制剂有关的最新发现，以及如何将这些分子用于未来的治疗策略。