Dominguez J A J, Luque-Vilca O M, Mallma N E S, FLores D D C, Zea C Y H, Huayhua L L A, Lizárraga-Gamarra F B, Cáceres C G M, Yauricasa-Tornero S V, Paricanaza-Ticona D C, Cajavilca H L V
Universidad Nacional de Piura, Piura, Perú.
Universidad Nacional de Juliaca, Juliaca, Perú.
Braz J Biol. 2024 Feb 23;83:e275055. doi: 10.1590/1519-6984.275055. eCollection 2024.
The increasing use of antimicrobial drugs has been linked to the rise of drug-resistant fungus in recent years. Antimicrobial resistance is being studied from a variety of perspectives due to the important clinical implication of resistance. The processes underlying this resistance, enhanced methods for identifying resistance when it emerges, alternate treatment options for infections caused by resistant organisms, and so on are reviewed, along with strategies to prevent and regulate the formation and spread of resistance. This overview will focus on the action mechanism of antifungals and the resistance mechanisms against them. The link between antibacterial and antifungal resistance is also briefly discussed. Based on their mechanism action, antifungals are divided into three distinct categories: azoles, which target the ergosterol synthesis; 5-fluorocytosine, which targets macromolecular synthesis and polyenes, which interact physiochemically with fungal membrane sterols. Antifungal resistance can arise through a wide variety of ways. Overexpression of the target of the antifungal drug, changes to the drug target, changes to sterol biosynthesis, decreased intercellular concentration of the target enzyme, and other processes. A correlation exists between the mechanisms of resistance to antibacterial and antifungals, despite the fact that the comparison between the two is inevitably constrained by various parameters mentioned in the review. Drug extrusion via membrane pumps has been thoroughly documented in both prokaryotic and eukaryotic cells, and development of new antifungal compounds and strategies has also been well characterized.
近年来,抗菌药物使用的增加与耐药真菌的增多有关。由于耐药性具有重要的临床意义,因此正在从多种角度对抗菌药物耐药性进行研究。本文回顾了耐药性产生的潜在过程、耐药性出现时的增强识别方法、耐药菌引起感染的替代治疗选择等内容,以及预防和控制耐药性形成与传播的策略。本综述将重点关注抗真菌药物的作用机制及其耐药机制。同时也简要讨论了抗菌耐药性与抗真菌耐药性之间的联系。根据作用机制,抗真菌药物可分为三大类:作用于麦角固醇合成的唑类;作用于大分子合成的5-氟胞嘧啶;以及与真菌细胞膜固醇发生物理化学相互作用的多烯类。抗真菌耐药性可通过多种方式产生。包括抗真菌药物靶点的过表达、药物靶点的改变、固醇生物合成的改变、靶酶细胞内浓度的降低等过程。尽管抗菌耐药性和抗真菌耐药性机制之间的比较不可避免地受到本综述中提到的各种参数的限制,但两者之间仍存在相关性。通过膜泵进行药物外排已在原核细胞和真核细胞中得到充分证明,新型抗真菌化合物和策略的开发也已得到充分表征。