Ciociola Tecla, Giovati Laura, Conti Stefania, Magliani Walter
Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy.
Microorganisms. 2021 Jan 10;9(1):143. doi: 10.3390/microorganisms9010143.
Mycoses still represent relevant opportunistic infections worldwide, although overshadowed in recent years by other severe and more widespread infections. Moreover, deep-seated mycoses are often accompanied by unacceptably high mortality rates. Etiologic agents include endogenous components of the mycobiota, and species above all, and exogenous species, both yeasts and filamentous fungi. Old and new fungal pathogens are increasingly characterized by resistance to the existing antifungal agents, making imperative the search for effective and safe new therapeutics. Among the candidate molecules proposed in recent decades, synthetic peptides derived from the complementarity determining and constant regions of diverse antibodies (Abs), as well as the translated products of Ab-encoding genes, have proved of considerable interest. Their anti-infective activities, regardless of the specificity and isotype of the originating Ab, will be briefly presented and discussed in the light of their different mechanisms of action. Intriguing suggestions on the possible function of Abs after their half-life will be presented, following the recent detection, in human serum, of an antimicrobial Ab-derived peptide. Overall, Abs could represent a source of biologically active, highly flexible peptides, devoid of detectable toxicity, which can be easily synthesized and manipulated to be used, alone or in association with already available drugs, for new anti-infective strategies.
真菌病在全球范围内仍然是重要的机会性感染,尽管近年来被其他严重且更广泛传播的感染所掩盖。此外,深部真菌病往往伴随着高得令人难以接受的死亡率。病原体包括真菌群落的内源性成分,尤其是念珠菌属,以及外源性菌种,包括酵母菌和丝状真菌。新老真菌病原体越来越多地表现出对现有抗真菌药物的耐药性,因此寻找有效且安全的新疗法迫在眉睫。在近几十年提出的候选分子中,源自不同抗体(Ab)互补决定区和恒定区的合成肽,以及Ab编码基因的翻译产物,已证明具有相当大的研究价值。将根据其不同的作用机制简要介绍和讨论它们的抗感染活性,而不考虑起始Ab的特异性和同种型。继最近在人血清中检测到一种抗菌Ab衍生肽之后,将提出关于Ab半衰期后可能功能的有趣见解。总体而言,Ab可能代表一种具有生物活性、高度灵活的肽源,没有可检测到的毒性,易于合成和操作,可单独使用或与现有药物联合使用,用于新的抗感染策略。