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大量小鼠单克隆抗体揭示了伯克霍尔德菌属假鼻疽杆菌和鼻疽杆菌的抗原性与致病性之间的关系。

Relationship between antigenicity and pathogenicity for Burkholderia pseudomallei and Burkholderia mallei revealed by a large panel of mouse MAbs.

作者信息

Zou Nianxiang, Tsai Shien, Feng Shaw-Huey, Newsome Tamara, Kim Hyung-Yong, Li Bingjie, Zhang Shimin, Lo Shyh-Ching

机构信息

Department of Environmental and Infectious Disease Sciences, American Registry of Pathology, Armed Forces Institute of Pathology, Washington, DC 20306, USA.

出版信息

Hybridoma (Larchmt). 2008 Aug;27(4):231-40. doi: 10.1089/hyb.2008.0012.

Abstract

Burkholderia pseudomallei and Burkholderia mallei are two closely related gram-negative bacterial species classified by the CDC as category B biowarfare agents. To develop monoclonal antibodies (MAbs) that can recognize as many different strains and/or clinical isolates of these two pathogens as possible, we immunized mice with heat-killed bacterial whole cells and membrane preparations from multiple strains and/or clinical isolates of B. pseudomallei and B. mallei. More than 100 different hybridoma clones that produced MAbs strongly reacting to B. pseudomallei and/or B. mallei have been developed. These MAbs were categorized into eight different groups according to their reaction specificity against different species of Burkholderia bacteria as well as the different nature of target antigens (LPS, capsule polysaccharides, proteins, and glycoproteins) on the bacteria they recognized. Characterization of this large panel of MAbs has demonstrated an interesting pattern of various antigenic epitopes shared by the different species of Burkholderia bacteria. More importantly, this study has revealed a pathogenicity-linked antigen epitope(s) on capsule-like polysaccharides found only in the pathogenic species of Burkholderia bacteria and a Burkholderia-specific antigen epitope(s) that did not exist in other gram-negative bacterial species. Our MAbs should prove to be highly valuable in the development of detection, diagnosis, and therapeutic applications against B. mallei and B. pseudomallei infections.

摘要

伯克霍尔德氏菌属假鼻疽杆菌和鼻疽杆菌是两种密切相关的革兰氏阴性细菌,美国疾病控制与预防中心将它们列为B类生物战剂。为了开发能够识别这两种病原体尽可能多的不同菌株和/或临床分离株的单克隆抗体(MAb),我们用来自多种假鼻疽杆菌和鼻疽杆菌菌株和/或临床分离株的热灭活细菌全细胞和膜制剂免疫小鼠。现已开发出100多个产生对假鼻疽杆菌和/或鼻疽杆菌有强烈反应的单克隆抗体的不同杂交瘤克隆。这些单克隆抗体根据它们对不同伯克霍尔德氏菌属细菌的反应特异性以及它们所识别细菌上靶抗原(脂多糖、荚膜多糖、蛋白质和糖蛋白)的不同性质,被分为八个不同的组。对这一大批单克隆抗体的表征揭示了不同伯克霍尔德氏菌属细菌共有的各种抗原表位的有趣模式。更重要的是,本研究揭示了仅在伯克霍尔德氏菌属致病菌种中发现的类荚膜多糖上与致病性相关的抗原表位以及在其他革兰氏阴性细菌种中不存在的伯克霍尔德氏菌属特异性抗原表位。我们的单克隆抗体在针对鼻疽杆菌和假鼻疽杆菌感染的检测、诊断和治疗应用开发中应具有很高的价值。

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