多重耐药真菌的出现令人严重关切,其感染是导致免疫功能低下患者大量死亡的原因。真菌感染的治疗主要依赖于临床一类抗生素,包括唑类,多烯,棘白菌素,聚酮化合物,和核苷酸类似物。然而,随着人类和植物真菌感染的治疗与抗真菌药物重叠,真菌感染的发生率正在增加。对作用于不同于已知靶标的靶标的新抗真菌剂的需求是不可否认的。此外,不能破坏真菌对抗生素敏感性丧失的速度。真菌可以通过几种模式产生对抗生素的抗性,包括减少药物摄取,药物靶点改变,以及由于活性挤出和生物膜形成而导致的药物细胞浓度降低。真菌外排泵的过度表达主要将抗生素的浓度降低至亚致死浓度,从而负责开发抗性真菌菌株。几种策略用于检查多药耐药真菌的抗生素耐药性,包括合成抗生素类似物和在联合疗法中给予抗生素。其中外排泵蛋白抑制剂被认为是抗生素的潜在佐剂,可以通过抑制外排泵蛋白转运蛋白来阻断抗生素的外排。此外,它可以使抗真菌药物对具有过度表达的外排泵蛋白的多药耐药真菌敏感。这篇综述讨论了天然铅分子,可重复使用的药物,和制定策略来克服真菌中的外排泵活性。
The emergence of multidrug-resistant fungi is of grave concern, and its infections are responsible for significant deaths among immunocompromised patients. The treatment of fungal infections primarily relies on a clinical class of antibiotics, including azoles,
polyenes, echinocandins, polyketides, and a nucleotide analogue. However, the incidence of fungal infections is increasing as the treatment for human and plant fungal infections overlaps with antifungal drugs. The need for new antifungal agents acting on different targets than known targets is undeniable. Also, the pace at which loss of fungal susceptibility to antibiotics cannot be undermined. There are several modes by which fungi can develop resistance to antibiotics, including reduced drug uptake, drug target alteration, and a reduction in the cellular concentration of the drug due to active extrusions and biofilm formation. The efflux pump\'s overexpression in the fungi primarily reduced the antibiotic\'s concentration to a sub-lethal concentration, thus responsible for developing resistant fungus strains. Several strategies are used to check antibiotic resistance in multi-drug resistant fungi, including synthesizing antibiotic analogs and giving antibiotics in combination therapies. Among them, the efflux pump protein inhibitors are considered potential adjuvants to antibiotics and can block the efflux of antibiotics by inhibiting efflux pump protein transporters. Moreover, it can sensitize the antifungal drugs to multi-drug resistant fungi with overexpressed efflux pump proteins. This review discusses the natural lead molecules, repurposable drugs, and formulation strategies to overcome the efflux pump activity in the fungi.