真菌耐药的分子机制及新型抗真菌药物

真菌耐药性的发生率日益增多,严重影响了抗真菌药物的治疗效果。在分子水平上了解真菌耐药性的发生机制对控制其耐药性的发展和新型抗真菌药物的研究和开发十分重要。本文介绍了近年来真菌耐药性研究的新进展,以及目前正处于研究阶段的新型抗真菌药物。     

抗真菌肽对真菌作用机制研究进展

20 世纪 90 年代初, Iijima 等从麻蝇幼虫血淋巴分离出一种具有抗真菌活性、能抑制 C.albicans 生长的蛋白质 . 到目前为止,已发现 150 多种肽具有抗真菌的特性,随着被发现的抗真菌肽数目不断增多,人们对抗真菌肽的抗真菌机理也进行了大量的研究,抗真菌肽对真菌的作用方式主要有：阻止、破坏真菌细胞壁的合成;与膜作用,在质膜上形成孔洞,使重要的内容物外泄;与真菌细胞内线粒体、核酸大分子等重要细胞器相互作用;最终导致真菌的死亡 .     

纳米材料的抗真菌活性及其机制研究进展

随着抗真菌药物的广泛使用,真菌的耐药性明显增强,这使科学家将目光转向了基本不产生耐药性、安全性更高的纳米材料.目前,应用比较广泛的主要有金属型纳米抗真菌材料、光催化型抗真菌材料及复合型抗真菌材料.本文综合近几年的研究报道,简要叙述不同纳米材料的抗真菌活性及其机制.     

山苍子油抗真菌的研究进展

山苍子油是从中药山苍子中提炼的精油,一直作为香料供应市场,近几年研究表明山苍子油具有广谱抗真菌作用。针对近年来真菌病发病率升高、真菌耐药性增加及抗真菌药物毒副作用多等现象,开发研究一种高效、广谱、较少耐药、价格低廉的抗真菌药物已成为一个亟待解决的问题,因此抗真菌中药的研究受到越来越多医药工作者的重视。本文介绍了近年来山苍子油抗真菌的研究进展,以期对新抗真菌药物的研究有所帮助。     

抗真菌药物增效剂的研究进展

近年来,真菌耐药发生率呈逐年上升趋势,真菌对氟康唑等氮唑类药物的耐药性最为严重,成为临床抗真菌治疗失败的原因之一.对于耐药真菌的治疗,往往采用加大剂量或联合用药的方法.此外,文献报道了一些植物提取物、小分子化合物能显著增强抗真菌药物对耐药真菌的敏感性,两个药物的协同作用有望成为治疗耐药真菌的新策略.该文结合近几年的研究报道,简要综述了抗真菌药物增效剂的研究进展.     

抗真菌药物及其作用机制研究

由于唑类药物长期使用,真菌耐药性及其交叉耐药现象不断出现,对临床治疗具有重要威胁。近年来提出新型抗真菌药物的新靶点,并研发出具有高活性强、强疗效的抗真菌药物。本研究对近年来新型抗真菌药的种类、结构和特点进行阐述,并介绍不同型药物对真菌的细胞壁、细胞膜、蛋白质合成、呼吸链等作用新靶点和作用机制的研究进展。     

白念珠菌生物膜耐药机制及中药治疗的研究进展

近几年来,由于临床诊治时滥用抗生素、糖皮质激素等药物,导致各种真菌对抗真菌药物的耐药性日渐增强,后续治疗可供选择药物愈来愈少,这类真菌感染性问题的解决迫在眉睫。临床上经常使用的抗真菌药物主要有氟康唑、伏立康唑、酮康唑等。其中氟康唑常被选作治疗真菌感染的药物,但长期使用,不但会导致耐药性大大增加,而且在耐受氟康唑类药物后真菌也会对其他抗真菌药物产生一系列交叉耐药性[1]。因此,目前有许多中药研究是在与氟康唑类药物协同作用的基础上进行抗耐药试验的[2-5]。     

两性霉素B抗真菌作用机制与病原性土曲霉对其耐药机制的研究进展

两性霉素B(amphotericin B,AMB)是经典的多烯类抗真菌药物,对病原真菌具有广谱抗菌活性,且不易产生耐药性.土曲霉是临床上常见的病原性曲霉,因其对AMB天然耐药而受到关注.现阶段,AMB的抗真菌作用机制有待进一步阐明,且真菌对AMB的耐药机制研究亦不充分.本文就AMB在土曲霉中诱导内源性活性氧(react...     

光动力疗法在真菌感染性疾病中的应用

随着激素、广谱抗生素和免疫抑制剂在临床上的广泛应用,真菌感染的发病率不断上升,加上真菌耐药性日趋严重,使得抗真菌药物治疗面临的挑战越来越大.光动力疗法是一种具有高度选择性的药械联动技术,越来越多的研究表明光动力疗法能有效对抗念珠菌、马拉色菌等真菌性疾病的感染,该文就光动力疗法的特点以及光动力学疗法治疗真菌感染的现状做一综述,旨在让大家对光动力抗真菌治疗有一个全面深入的了解.     

真菌的多向耐药性ABC转运蛋白

真菌的多向耐药性ABC转运蛋白(ATP-binding cassette transporters)是导致多药耐药性和抗真菌药物治疗效果明显下降的主要原因。文章对酿酒酵母(Saccharomyces cerevisiae)和主要致病真菌白色假丝酵母(Candida albicans)、新型隐球酵母(Cryptococcus neoformans)和烟曲霉(Aspergillus fumigatus)中的多向耐药性ABC转运蛋白的种类、药物外排机制以及基因表达调控网络的研究进展作一综述,为深入了解真菌的多向耐药性机制以及探讨克服多向耐药性的策略和提高药效提供参考。     

Antifungal proteins and peptides of leguminous and non-leguminous origins

Antifungal proteins and peptides, as their names imply, serve a protective function against fungal invasion. They are produced by a multitude of organisms including leguminous flowering plants, non-leguminous flowering plants, gymnosperms, fungi, bacteria, insects and mammals. The intent of the present review is to focus on the structural and functional characteristics of leguminous, as well as non-leguminous, antifungal proteins and peptides. A spectacular diversity of amino acid sequences has been reported. Some of the antifungal proteins and peptides are classified, based on their structures and/or functions, into groups including chitinases, glucanases, thaumatin-like proteins, thionins, and cyclophilin-like proteins. Some of the well-known proteins such as lectins, ribosome inactivating proteins, ribonucleases, deoxyribonucleases, peroxidases, and protease inhibitors exhibit antifungal activity. Different antifungal proteins may demonstrate different fungal specificities. The mechanisms of antifungal action of only some antifungal proteins including thaumatin-like proteins and chitinases have been elucidated.     

Toward a clinical antifungal peptoid: Investigations into the therapeutic potential of AEC5

Cryptococcus neoformans is a fungal pathogen that causes cryptococcal meningitis in immunocompromised individuals. Existing antifungal treatment plans have high mammalian toxicity and increasing drug resistance, demonstrating the dire need for new, nontoxic therapeutics. Antimicrobial peptoids are one alternative to combat this issue. Our lab has recently identified a tripeptoid, AEC5, with promising efficacy and selectivity against C. neoformans. Here, we report studies into the broad-spectrum efficacy, killing kinetics, mechanism of action, in vivo half-life, and subchronic toxicity of this compound. Most notably, these studies have demonstrated that AEC5 rapidly reduces fungal burden, killing all viable fungi within 3 hours. Additionally, AEC5 has an in vivo half-life of 20+ hours and no observable in vivo toxicity following 28 days of daily injections. This research represents an important step in the characterization of AEC5 as a practical treatment option against C. neoformans infections.     

An overview of antifungal peptides derived from insect

Fungi are not classified as plants or animals. They resemble plants in many ways but do not produce chlorophyll or make their own food photosynthetically like plants. Fungi are useful for the production of beer, bread, medicine, etc. More complex than viruses or bacteria; fungi can be destructive human pathogens responsible for various diseases in humans. Most people have a strong natural immunity against fungal infection. However, fungi can cause diseases when this immunity breaks down. In the last few years, fungal infection has increased strikingly and has been accompanied by a rise in the number of deaths of cancer patients, transplant recipients, and acquired immunodeficiency syndrome (AIDS) patients owing to fungal infections. The growth rate of fungi is very slow and quite difficult to identify. A series of molecules with antifungal activity against different strains of fungi have been found in insects, which can be of great importance to tackle human diseases. Insects secrete such compounds, which can be peptides, as a part of their immune defense reactions. Active antifungal peptides developed by insects to rapidly eliminate infectious pathogens are considered a component of the defense munitions. This review focuses on naturally occurring antifungal peptides from insects and their challenges to be used as armaments against human diseases.     

天然化合物抗真菌活性研究进展

近年来,真菌感染患者的发病率和死亡率持续上升,但现有抗真菌药物种类依然非常少,并且耐药现象的出现使临床可选择的抗真菌药物变得更加有限.因此,对新的抗真菌药物的开发迫在眉睫,从天然产物中寻找新型高效的抗真菌药物成为目前的研究热点之一.从天然产物中筛选出具有抗真菌活性的天然化合物,有助于扩大治疗真菌感染疾病的可选药物种类,减少耐药的发生.该文归纳现有报道的具有抗真菌活性的化合物,根据其不同来源及不同化学结构进行分类,阐明不同类别天然化合物的抗真菌作用机制,为开发新型高效抗真菌药物提供前体结构及抗真菌新靶点.     

新的抗真菌药物靶点研究进展

近30年来,侵袭性真菌感染发病率持续上升,病死率居高不下,而治疗药物十分有限是造成其高致死率的重要因素之一。因此,发现新的抗真菌靶点和药物,已成为迫切需要。正在研究的新的抗真菌靶点如下：一是信号通路介导的抗真菌靶点,包括钙调神经磷酸酶及其分子伴侣Hsp90、3-磷酸肌醇依赖性蛋白激酶（PKH）以及参与Ras蛋白修饰的相关酶等,其拮抗剂包括传统免疫抑制剂的类似物以及Hsp90抗体、KP-372-1和PS77以及手霉素A等;二是GPI锚定蛋白合成通路的催化酶,其抑制剂有E1210和M720等化合物;三是分泌型天冬氨酸蛋白酶,肽类、逆转录病毒抑制剂,以及砜类的衍生物等均可以抑制这一靶点;四是海藻糖的合成的两个关键酶Tps1和Tps2。鉴于侵袭性真菌感染严重影响人类公共健康安全,而新型抗真菌药物的研发又依赖于新靶点的探索,因此,本文靶向这一核心真菌临床问题,系统介绍了当前新的抗真菌药物靶点发展概况,并在靶点选择可行性以及针对靶点的药物研发策略上提出见解。