Oshiro Karen G N, Rodrigues Gisele, Monges Bruna Estéfani D, Cardoso Marlon Henrique, Franco Octávio Luiz
Programa de Pós-Graduação em Patologia Molecular, Faculdade de Medicina, Universidade de Brasília, Brasília, Brazil.
S-Inova Biotech, Programa de Pós-Graduação em Biotecnologia, Universidade Católica Dom Bosco, Campo Grande, Brazil.
Front Microbiol. 2019 Oct 4;10:2169. doi: 10.3389/fmicb.2019.02169. eCollection 2019.
Infections caused by invasive fungal biofilms have been widely associated with high morbidity and mortality rates, mainly due to the advent of antibiotic resistance. Moreover, fungal biofilms impose an additional challenge, leading to multidrug resistance. This fact, along with the contamination of medical devices and the limited number of effective antifungal agents available on the market, demonstrates the importance of finding novel drug candidates targeting pathogenic fungal cells and biofilms. In this context, an alternative strategy is the use of antifungal peptides (AFPs) against fungal biofilms. AFPs are considered a group of bioactive molecules with broad-spectrum activities and multiple mechanisms of action that have been widely used as template molecules for drug design strategies aiming at greater specificity and biological efficacy. Among the AFP classes most studied in the context of fungal biofilms, defensins, cathelicidins and histatins have been described. AFPs can also act by preventing the formation of fungal biofilms and eradicating preformed biofilms through mechanisms associated with cell wall perturbation, inhibition of planktonic fungal cells' adhesion onto surfaces, gene regulation and generation of reactive oxygen species (ROS). Thus, considering the critical scenario imposed by fungal biofilms and associated infections and the application of AFPs as a possible treatment, this review will focus on the most effective AFPs described to date, with a core focus on antibiofilm peptides, as well as their efficacy , application on surfaces and proposed mechanisms of action.
侵袭性真菌生物膜引起的感染与高发病率和死亡率广泛相关,主要是由于抗生素耐药性的出现。此外,真菌生物膜带来了额外的挑战,导致多药耐药。这一事实,连同医疗器械的污染以及市场上可用的有效抗真菌药物数量有限,都表明了寻找针对致病真菌细胞和生物膜的新型候选药物的重要性。在这种背景下,一种替代策略是使用抗真菌肽(AFP)来对抗真菌生物膜。AFP被认为是一类具有广谱活性和多种作用机制的生物活性分子,已被广泛用作药物设计策略的模板分子,旨在实现更高的特异性和生物学功效。在真菌生物膜背景下研究最多的AFP类别中,已描述了防御素、cathelicidin和组蛋白。AFP还可以通过与细胞壁扰动、抑制浮游真菌细胞在表面的粘附、基因调控和活性氧(ROS)生成相关的机制来防止真菌生物膜的形成并根除预先形成的生物膜。因此,考虑到真菌生物膜和相关感染所带来的严峻情况以及AFP作为一种可能的治疗方法的应用,本综述将聚焦于迄今为止描述的最有效的AFP,核心关注抗生物膜肽,以及它们的功效、在表面的应用和提出的作用机制。