a Department of Biotechnology and Microbiology , University of Debrecen , Debrecen , Hungary.
b Department of Physiology , University of Debrecen , Debrecen , Hungary.
Expert Opin Ther Targets. 2018 Dec;22(12):1039-1048. doi: 10.1080/14728222.2018.1541087. Epub 2018 Oct 30.
Diseases caused by pathogenic fungi are increasing because of antibiotic overuse, the rise of immunosuppressive therapies, and climate change. The limited variety of antimycotics and the rapid adaptation of pathogenic fungi to antifungal agents serve to exacerbate this issue. Unfortunately, about 1.6 million people are killed by fungal infections annually. Areas covered: The discovery of the small antimicrobial proteins produced by microorganisms, animals, humans, and plants will hopefully overcome challenges in the treatment of fungal infections. These small proteins are highly stable and any resistance to them rarely evolves; therefore, they are potentially good candidates for the treatment and prevention of infections caused by pathogenic fungi. Some of these proteins target the programmed cell death machinery of pathogenic fungi; this is potentially a novel approach in antimycotic therapies. In this review, we highlight the elements of apoptosis in human pathogenic fungi and related model organisms and discuss the possible therapeutic potential of the apoptosis-inducing, small, antifungal proteins. Expert opinion: Small antimicrobial proteins may establish a new class of antimycotics in the future. The rarity of resistance and their synergistic effects with other frequently used antifungal agents may help pave the way for their use in the clinic.
由于抗生素滥用、免疫抑制疗法的兴起和气候变化，由致病真菌引起的疾病正在增加。抗真菌药物的种类有限，以及致病真菌对抗真菌药物的快速适应，进一步加剧了这一问题。不幸的是，每年约有 160 万人死于真菌感染。涵盖领域：发现微生物、动物、人类和植物产生的小型抗菌蛋白有望克服治疗真菌感染的挑战。这些小蛋白高度稳定，对它们几乎不会产生任何耐药性；因此，它们是治疗和预防致病性真菌感染的潜在良好候选物。其中一些蛋白针对致病真菌的程序性细胞死亡机制；这可能是抗真菌治疗的一种新方法。在这篇综述中，我们强调了人类致病性真菌和相关模式生物中细胞凋亡的要素，并讨论了诱导细胞凋亡的、具有抗真菌作用的小蛋白的可能治疗潜力。专家意见：小型抗菌蛋白可能会在未来开创一类新型抗真菌药物。耐药性罕见，以及它们与其他常用抗真菌药物的协同作用，可能有助于为它们在临床上的应用铺平道路。
