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首页> 外文期刊>Microbial Pathogenesis >Polymorphisms in the Pseudomonas aeruginosa type III secretion protein, PcrV - Implications for anti-PcrV immunotherapy
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Polymorphisms in the Pseudomonas aeruginosa type III secretion protein, PcrV - Implications for anti-PcrV immunotherapy

机译:铜绿假单胞菌III型分泌蛋白PcrV中的多态性-抗PcrV免疫疗法的意义

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摘要

The type III secretion system of Pseudomonas aeruginosa, responsible for acute infection, is composed of over twenty proteins that facilitate cytotoxin injection directly into host cells. Integral to this process is production and secretion of PcrV. Administration of a recently developed, anti-PcrV immunoglobulin, either as a therapeutic or prophylactic has previously demonstrated efficacy against laboratory strains of P. aeruginosa in a murine model. To determine if this therapy is universally applicable to a variety of P. aeruginosa clinical isolates, genetic heterogeneity of pcrV was analyzed among strains collected from three geographically distinct regions; United States, France and Japan. Sequence analysis of PcrV demonstrated limited variation among the clinical isolates examined. Strains were grouped according to the presence of non-synonymous single nucleotide polymorphisms. Representative isolates from each mutant group were examined for the ability of anti-PcrV to bind the protein secreted by these strains. The protective effect of anti-PcrV IgG against each strain was determined using an epithelial cell line cytotoxicity assay. The majority of strains tested demonstrated reduced cytotoxicity in the presence of anti-PcrV IgG. This study provides insights into the natural sequence variability of PcrV and an initial indication of the amino acid residues that appear to be conserved across strains. It also demonstrates the protective effect of anti-PcrV immunotherapy against a multitude of P. aeruginosa strains from diverse global regions with a variety of mutations in PcrV. (C) 2010 Elsevier Ltd. All rights reserved.
机译:负责急性感染的铜绿假单胞菌的III型分泌系统由二十多种蛋白质组成,这些蛋白质有助于将细胞毒素直接注射到宿主细胞中。 PcrV的产生和分泌是该过程不可或缺的部分。先前已证明,作为治疗剂或预防剂,施用最近开发的抗PcrV免疫球蛋白对鼠模型中的铜绿假单胞菌实验室菌株有效。为了确定这种疗法是否普遍适用于多种铜绿假单胞菌临床分离株,在从三个地理上不同的地区收集的菌株中分析了pcrV的遗传异质性。美国,法国和日本。 PcrV的序列分析表明,在所检查的临床分离株之间变异有限。根据非同义单核苷酸多态性的存在将菌株分组。检查来自每个突变组的代表性分离株抗PcrV结合这些菌株分泌的蛋白质的能力。使用上皮细胞系细胞毒性测定法确定抗PcrV IgG对每种菌株的保护作用。在抗PcrV IgG存在下,大多数测试菌株显示出降低的细胞毒性。这项研究提供了对PcrV的自然序列变异性的见解,并初步显示了似乎在所有菌株中都保守的氨基酸残基。它还证明了抗PcrV免疫疗法对来自不同全球地区的大量铜绿假单胞菌菌株具有PcrV突变的保护作用。 (C)2010 Elsevier Ltd.保留所有权利。

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