Abstract:
Antimicrobial resistance (AMR) is a growing concern because it causes microorganisms to develop resistance to drugs commonly used to treat infections. This results in increased difficulty in treating infections, leading to higher mortality rates and significant economic effects. Investing in new antimicrobial agents is, therefore, necessary to prevent and control AMR. Antimicrobial nucleic acids have arisen as potential key players in novel therapies for AMR infections. They have been designed to serve as antimicrobials and to act as adjuvants to conventional antibiotics or to inhibit virulent mechanisms. This new category of antimicrobial drugs consists of antisense oligonucleotides and oligomers, DNAzymes, and transcription factor decoys, differing in terms of structure, target molecules, and mechanisms of action. They are synthesized using nucleic acid analogs to enhance their resistance to nucleases. Because bacterial envelopes are generally impermeable to oligonucleotides, delivery into the cytoplasm typically requires the assistance of nanocarriers, which can affect their therapeutic potency. Given that numerous factors contribute to the success of these antimicrobial drugs, this review aims to provide a summary of the key advancements in the use of oligonucleotides for treating bacterial infections. Their mechanisms of action and the impact of factors such as nucleic acid design, target sequence, and nanocarriers on the antimicrobial potency are discussed.
摘要:
抗菌素耐药性(AMR)是一个日益关注的问题,因为它导致微生物对通常用于治疗感染的药物产生耐药性。这导致治疗感染的难度增加,导致更高的死亡率和显著的经济影响。投资新的抗菌剂是,因此,必须预防和控制AMR。抗微生物核酸已经成为AMR感染的新疗法中的潜在关键参与者。它们已被设计为用作抗微生物剂并用作常规抗生素的佐剂或抑制毒力机制。这类新型抗菌药物由反义寡核苷酸和寡聚体组成,DNAzyme,和转录因子诱饵,在结构上不同,靶分子,和行动机制。使用核酸类似物合成它们以增强它们对核酸酶的抗性。因为细菌包膜通常对寡核苷酸是不可渗透的,传递到细胞质中通常需要纳米载体的帮助,这会影响他们的治疗效力。鉴于许多因素有助于这些抗菌药物的成功,本综述旨在总结使用寡核苷酸治疗细菌感染的关键进展。它们的作用机制和核酸设计等因素的影响,靶序列,并讨论了纳米载体对抗菌效力的影响。