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一种针对白色念珠菌细胞壁甘露糖蛋白的单克隆抗体具有三种抗白色念珠菌活性。

A monoclonal antibody directed against a Candida albicans cell wall mannoprotein exerts three anti-C. albicans activities.

作者信息

Moragues María D, Omaetxebarria Miren J, Elguezabal Natalia, Sevilla María J, Conti Stefania, Polonelli Luciano, Pontón José

机构信息

Departamento de Enfermería I, Universidad del País Vasco, E-48080 Bilbao, Vizcaya, Spain.

出版信息

Infect Immun. 2003 Sep;71(9):5273-9. doi: 10.1128/IAI.71.9.5273-5279.2003.

Abstract

Antibodies are believed to play a role in the protection against Candida albicans infections by a number of mechanisms, including the inhibition of adhesion or germ tube formation, opsonization, neutralization of virulence-related enzymes, and direct candidacidal activity. Although some of these biological activities have been demonstrated individually in monoclonal antibodies (MAbs), it is not clear if all these anti-C. albicans activities can be displayed by a single antibody. In this report, we characterized a monoclonal antibody raised against the main target of salivary secretory immunoglobulin A in the cell wall of C. albicans, which exerts three anti-C. albicans activities: (i) inhibition of adherence to HEp-2 cells, (ii) inhibition of germination, and (iii) direct candidacidal activity. MAb C7 reacted with a proteinic epitope from a mannoprotein with a molecular mass of >200 kDa predominantly expressed on the C. albicans germ tube cell wall surface as well as with a number of antigens from Candida lusitaniae, Cryptococcus neoformans, Aspergillus fumigatus, and Scedosporium prolificans. MAb C7 caused a 31.1% inhibition in the adhesion of C. albicans to HEp-2 monolayers and a 55.3% inhibition in the adhesion of C. albicans to buccal epithelial cells, produced a 38.5% decrease in the filamentation of C. albicans, and exhibited a potent fungicidal effect against C. albicans, C. lusitaniae, Cryptococcus neoformans, A. fumigatus, and S. prolificans, showing reductions in fungal growth ranging from 34.2 to 88.7%. The fungicidal activity showed by MAb C7 seems to be related to that reported by antibodies mimicking the activity of a killer toxin produced by the yeast Pichia anomala, since one of these MAbs also reacted with the C. albicans mannoprotein with a molecular mass of >200 kDa. Results presented in this study support the concept of a family of microbicidal antibodies that could be useful in the treatment of a wide range of microbial infections when used alone or in combination with current antimicrobial agents.

摘要

抗体被认为通过多种机制在抵御白色念珠菌感染中发挥作用,这些机制包括抑制黏附或芽管形成、调理作用、中和与毒力相关的酶以及直接的杀念珠菌活性。尽管其中一些生物学活性已在单克隆抗体(MAb)中分别得到证实,但尚不清楚是否所有这些抗白色念珠菌活性都能由单一抗体展现出来。在本报告中,我们鉴定了一种针对白色念珠菌细胞壁中唾液分泌型免疫球蛋白A主要靶点产生的单克隆抗体,该抗体具有三种抗白色念珠菌活性:(i)抑制对HEp - 2细胞的黏附,(ii)抑制芽管形成,以及(iii)直接的杀念珠菌活性。单克隆抗体C7与一种分子量>200 kDa的甘露糖蛋白的蛋白质表位发生反应,该甘露糖蛋白主要表达于白色念珠菌芽管细胞壁表面,同时还与葡萄牙念珠菌、新型隐球菌、烟曲霉和多育赛多孢菌的多种抗原发生反应。单克隆抗体C7使白色念珠菌对HEp - 2单层细胞的黏附抑制了31.1%,对颊上皮细胞的黏附抑制了55.3%,使白色念珠菌的菌丝形成减少了38.5%,并对白色念珠菌、葡萄牙念珠菌、新型隐球菌、烟曲霉和多育赛多孢菌表现出强大的杀真菌作用,真菌生长减少幅度在34.2%至88.7%之间。单克隆抗体C7所显示的杀真菌活性似乎与模仿酵母异常毕赤酵母产生的杀伤毒素活性的抗体所报告的活性有关,因为这些单克隆抗体之一也与分子量>200 kDa的白色念珠菌甘露糖蛋白发生反应。本研究结果支持了一类杀菌抗体的概念,这类抗体单独使用或与当前抗菌药物联合使用时,可能对治疗多种微生物感染有用。

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