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丝氨酸蛋白酶抑制剂 Ecotin 是伯克霍尔德氏菌完全毒力所必需的。

The serine protease inhibitor Ecotin is required for full virulence of Burkholderia pseudomallei.

机构信息

Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK.

Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK.

出版信息

Microb Pathog. 2014 Feb-Mar;67-68:55-8. doi: 10.1016/j.micpath.2014.01.001. Epub 2014 Jan 23.

Abstract

Burkholderia pseudomallei is a Gram negative soil saprophyte that causes the disease melioidosis where clinical symptoms can vary from localised infection to pneumonia and septic shock. Ecotin is a potent periplasmic serine protease inhibitor first identified in Escherichia coli. Ecotin, although present in only a small subset of genera, can inhibit a broad range of serine proteases including those typically associated with the innate immune system such as neutrophil elastase and cathepsin G. An Ecotin orthologue identified in B. pseudomallei was recombinantly expressed and found to inhibit elastase. To study the role of Ecotin in B. pseudomallei virulence an in-frame unmarked deletion mutant was created. Infection of a murine macrophages-like cell line revealed Ecotin was necessary for the early stages of colonisation allowing replication following cell entry. Attenuation of the Δeco mutant strain in the murine model of melioidosis further supported Ecotin as a virulence factor of B. pseudomallei.

摘要

类鼻疽伯克霍尔德菌是一种革兰氏阴性土壤腐生菌,可引起类鼻疽病,其临床症状从局部感染到肺炎和感染性休克不等。Ecotin 是一种强效的周质丝氨酸蛋白酶抑制剂,最初在大肠杆菌中被发现。Ecotin 虽然只存在于少数属中,但可以抑制广泛的丝氨酸蛋白酶,包括通常与先天免疫系统相关的蛋白酶,如中性粒细胞弹性蛋白酶和组织蛋白酶 G。在类鼻疽伯克霍尔德菌中鉴定出的 Ecotin 同源物被重组表达并发现能抑制弹性蛋白酶。为了研究 Ecotin 在类鼻疽伯克霍尔德菌毒力中的作用,构建了一个无标记缺失突变体。对鼠巨噬细胞样细胞系的感染表明 Ecotin 是定植早期所必需的,使其能够在细胞进入后进行复制。在类鼻疽病的小鼠模型中,Δeco 突变株的衰减进一步支持 Ecotin 是类鼻疽伯克霍尔德菌的毒力因子。

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