Abstract

Therapeutic options to treat invasive fungal infections are still limited. This makes the development of novel antifungal agents highly desirable. Naturally occurring antifungal peptides represent valid candidates, since they are not harmful for human cells and are endowed with a wide range of activities and their mechanism of action is different from that of conventional antifungal drugs. Here, we characterized for the first time the antifungal properties of novel peptides identified in human apolipoprotein B. ApoB-derived peptides, here named r(P)ApoB_L^Pro, r(P)ApoB_L^Ala and r(P)ApoB_S^Pro, were found to have significant fungicidal activity towards Candida albicans (C. albicans) cells. Peptides were also found to be able to slow down metabolic activity of Aspergillus niger (A. niger) spores. In addition, experiments were carried out to clarify the mechanism of fungicidal activity of ApoB-derived peptides. Peptides immediately interacted with C. albicans cell surfaces, as indicated by fluorescence live cell imaging analyses, and induced severe membrane damage, as indicated by propidium iodide uptake induced upon treatment of C. albicans cells with ApoB-derived peptides. ApoB-derived peptides were also tested on A. niger swollen spores, initial hyphae and branched mycelium. The effects of peptides were found to be more severe on swollen spores and initial hyphae compared to mycelium. Fluorescence live cell imaging analyses confirmed peptide internalization into swollen spores with a consequent accumulation into hyphae. Altogether, these findings open interesting perspectives to the application of ApoB-derived peptides as effective antifungal agents.

Key points

• Human cryptides identified in ApoB are effective antifungal agents.

• ApoB-derived cryptides exert fungicidal effects towards C. albicans cells.

• ApoB-derived cryptides affect different stages of growth of A. niger.

Graphical abstract

中文翻译：

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在人类载脂蛋白B中鉴定为有希望的抗真菌剂的宿主防御肽

摘要

侵袭性真菌感染的治疗选择仍然有限。这使得非常需要开发新型抗真菌剂。天然存在的抗真菌肽是有效的候选物，因为它们对人体细胞无害，并具有广泛的活性，并且其作用机理与常规抗真菌药物不同。在这里，我们首次表征了在人类载脂蛋白B中鉴定的新型肽的抗真菌特性。ApoB衍生的肽，在此命名为r（P）ApoB _L ^Pro，r（P）ApoB _L ^Ala和r（P）ApoB _S ^Pro被发现对白色念珠菌（白色念珠菌）具有显着的杀真菌活性。） 细胞。还发现肽能够减慢黑曲霉（A.niger）孢子的代谢活性。另外，进行实验以阐明ApoB衍生肽的杀真菌活性的机理。如荧光活细胞成像分析所示，肽立即与白色念珠菌细胞表面相互作用，并诱导严重的膜损伤，如用ApoB衍生肽处理白色念珠菌细胞后诱导的碘化丙啶摄取表明。ApoB衍生的肽也在黑曲霉上进行了测试孢子肿胀，最初的菌丝和分支的菌丝体。与菌丝体相比，发现肽对肿胀的孢子和初始菌丝的影响更为严重。荧光活细胞成像分析证实了肽内在化为肿胀的孢子，随后积累为菌丝。总之，这些发现为ApoB衍生肽作为有效的抗真菌剂的应用打开了有趣的前景。

关键点

• 在ApoB中鉴定的人类隐脂是有效的抗真菌药。

• ApoB衍生的隐秘剂对白色念珠菌细胞具有杀真菌作用。

• ApoB衍生的隐蛋白影响黑曲霉生长的不同阶段。

图形概要