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抗白色念珠菌铁通透酶Ftr1的IgY的制备及其以大蜡螟作为全身感染模型的抗真菌活性评估。

Production of IgY against iron permease Ftr1 from Candida albicans and evaluation of its antifungal activity using Galleria mellonella as a model of systemic infection.

作者信息

de Souza Patricia Canteri, Corrêa Alana Elke do Nascimento, Gameiro Juliana Gutschow, de Oliveira Júnior Admilton Gonçalves, Panagio Luciano Aparecido, Venancio Emerson José, Almeida Ricardo Sergio

机构信息

Department of Microbiology, Center of Biological Science, State University of Londrina, Rodovia Celso Garcia Cid, Pr 445, Km 380, Londrina, 86.057-970, Paraná, Brazil.

Department of Pathology, Clinical and Toxicological Analysis, Center of Health Sciences, State University of Londrina, Rodovia Celso Garcia Cid, Pr 445, Km 380, Londrina, 86.057-970, Paraná, Brazil.

出版信息

Microb Pathog. 2023 Aug;181:106166. doi: 10.1016/j.micpath.2023.106166. Epub 2023 Jun 7.

Abstract

Candida albicans is one of the leading pathological agents of mucosal and deep tissue infections. Considering that the variety of antifungals is restricted and that toxicity limits their use, immunotherapies against pathogenic fungi have been viewed as alternatives with reduced adverse effects. In this context, C. albicans has a protein used to capture iron from the environment and the host, known as the high-affinity iron permease Ftr1. This protein may be a new target of action for novel antifungal therapies, as it influences the virulence of this yeast. Thus, the aim of the present study was to produce and conduct the biological characterization of IgY antibodies against C. albicans Ftr1. Immunization of laying hens with an Ftr1-derived peptide resulted in IgY antibodies extracted from egg yolks capable of binding to the antigen with high affinity (avidity index = 66.6 ± 0.3%). These antibodies reduced the growth and even eliminated C. albicans under iron restriction, a favorable condition for the expression of Ftr1. This also occurred with a mutant strain that does not produce Ftr1 in the presence of iron, a circumstance in which the protein analog of iron permease, Ftr2, is expressed. Furthermore, the survival of G. mellonella larvae infected with C. albicans and treated with the antibodies was 90% higher than the control group, which did not receive treatment (p < 0.0001). Therefore, our data suggest that IgY antibodies against Ftr1 from C. albicans can inhibit yeast propagation by blocking iron uptake.

摘要

白色念珠菌是引起黏膜和深部组织感染的主要病原体之一。鉴于抗真菌药物种类有限且毒性限制了它们的使用,针对致病性真菌的免疫疗法被视为不良反应较少的替代方案。在此背景下,白色念珠菌有一种用于从环境和宿主体内摄取铁的蛋白质,称为高亲和力铁通透酶Ftr1。这种蛋白质可能是新型抗真菌疗法的新作用靶点,因为它影响这种酵母的毒力。因此,本研究的目的是制备并进行针对白色念珠菌Ftr1的IgY抗体的生物学特性研究。用Ftr1衍生肽免疫蛋鸡后,从蛋黄中提取的IgY抗体能够以高亲和力结合抗原(亲和力指数 = 66.6 ± 0.3%)。这些抗体在铁限制条件下(Ftr1表达的有利条件)可减少白色念珠菌的生长甚至将其消除。在铁存在的情况下,对于不产生Ftr1但表达铁通透酶蛋白类似物Ftr2的突变菌株,也会出现这种情况。此外,感染白色念珠菌并用抗体治疗的大蜡螟幼虫的存活率比未接受治疗的对照组高90%(p < 0.0001)。因此,我们的数据表明,针对白色念珠菌Ftr1的IgY抗体可通过阻断铁摄取来抑制酵母繁殖。

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