Polymorphisms in the Pseudomonas aeruginosa type III secretion protein, PcrV - implications for anti-PcrV immunotherapy.
Polymorphisms in the Pseudomonas aeruginosa type III secretion protein, PcrV - implications for anti-PcrV immunotherapy.
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DOI：
10.1016/j.micpath.2010.02.008
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发表时间：
2010-06
影响因子：
3.8
通讯作者：
Wiener-Kronish JP
中科院分区：
文献类型：
--
作者：
Lynch SV;Flanagan JL;Sawa T;Fang A;Baek MS;Rubio-Mills A;Ajayi T;Yanagihara K;Hirakata Y;Kohno S;Misset B;Nguyen JC;Wiener-Kronish JP
铜绿假单胞菌的III型分泌系统负责急性感染，由20多种促进细胞毒素直接注射到宿主细胞中的蛋白质组成。该过程的组成部分是PcrV的产生和分泌。施用最近开发的抗PcrV免疫球蛋白，无论是作为治疗性还是预防性，先前已经在鼠模型中证明了对铜绿假单胞菌实验室菌株的功效。为了确定这种疗法是否普遍适用于各种铜绿假单胞菌临床分离株，分析了从三个不同地理区域（美国、法国和日本）收集的菌株中pcrV的遗传异质性。PcrV的序列分析表明，有限的变化之间的临床分离株检查。根据非同义单核苷酸多态性的存在对菌株进行分组。检查来自每个突变组的代表性分离株的抗PcrV结合这些菌株分泌的蛋白的能力。使用上皮细胞系细胞毒性测定来确定抗PcrV IgG针对每种菌株的保护作用。测试的大多数菌株在抗PcrV IgG存在下表现出降低的细胞毒性。这项研究提供了深入了解PcrV的自然序列变异性和氨基酸残基的初步指示，似乎是保守的菌株。它还证明了抗PcrV免疫疗法对来自全球不同地区的具有各种PcrV突变的多种铜绿假单胞菌菌株的保护作用。
The type III secretion system of P. 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.
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