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对牛分枝杆菌 BCG Mexico 1931 的基因组和蛋白质组分析揭示了针对结核感染的多样化免疫原性谱。

Genomic and proteomic analyses of Mycobacterium bovis BCG Mexico 1931 reveal a diverse immunogenic repertoire against tuberculosis infection.

机构信息

Programa de Inmunología Molecular Microbiana, Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México, DF, México.

出版信息

BMC Genomics. 2011 Oct 8;12:493. doi: 10.1186/1471-2164-12-493.

DOI:10.1186/1471-2164-12-493
PMID:21981907
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3199284/
Abstract

BACKGROUND

Studies of Mycobacterium bovis BCG strains used in different countries and vaccination programs show clear variations in the genomes and immune protective properties of BCG strains. The aim of this study was to characterise the genomic and immune proteomic profile of the BCG 1931 strain used in Mexico.

RESULTS

BCG Mexico 1931 has a circular chromosome of 4,350,386 bp with a G+C content and numbers of genes and pseudogenes similar to those of BCG Tokyo and BCG Pasteur. BCG Mexico 1931 lacks Region of Difference 1 (RD1), RD2 and N-RD18 and one copy of IS6110, indicating that BCG Mexico 1931 belongs to DU2 group IV within the BCG vaccine genealogy. In addition, this strain contains three new RDs, which are 53 (RDMex01), 655 (RDMex02) and 2,847 bp (REDMex03) long, and 55 single-nucleotide polymorphisms representing non-synonymous mutations compared to BCG Pasteur and BCG Tokyo. In a comparative proteomic analysis, the BCG Mexico 1931, Danish, Phipps and Tokyo strains showed 812, 794, 791 and 701 protein spots, respectively. The same analysis showed that BCG Mexico 1931 shares 62% of its protein spots with the BCG Danish strain, 61% with the BCG Phipps strain and only 48% with the BCG Tokyo strain. Thirty-nine reactive spots were detected in BCG Mexico 1931 using sera from subjects with active tuberculosis infections and positive tuberculin skin tests.

CONCLUSIONS

BCG Mexico 1931 has a smaller genome than the BCG Pasteur and BCG Tokyo strains. Two specific deletions in BCG Mexico 1931 are described (RDMex02 and RDMex03). The loss of RDMex02 (fadD23) is associated with enhanced macrophage binding and RDMex03 contains genes that may be involved in regulatory pathways. We also describe new antigenic proteins for the first time.

摘要

背景

对不同国家和疫苗接种项目中使用的牛分枝杆菌卡介苗菌株的研究表明,卡介苗菌株的基因组和免疫保护特性存在明显差异。本研究旨在描述墨西哥使用的卡介苗 1931 株的基因组和免疫蛋白质组特征。

结果

BCG 墨西哥 1931 具有一个 4,350,386 bp 的圆形染色体,其 G+C 含量、基因和假基因数量与 BCG 东京和 BCG 巴斯德相似。BCG 墨西哥 1931 缺失 RD1、RD2 和 N-RD18 以及一个 IS6110 拷贝,表明 BCG 墨西哥 1931 属于卡介苗疫苗谱系中的 DU2 组 IV。此外,该菌株还含有三个新的 RD,分别长 53(RDMex01)、655(RDMex02)和 2,847 bp(REDMex03),与 BCG 巴斯德和 BCG 东京相比,有 55 个代表非同义突变的单核苷酸多态性。在比较蛋白质组分析中,BCG 墨西哥 1931、丹麦、菲普斯和东京菌株分别显示出 812、794、791 和 701 个蛋白质斑点。同样的分析表明,BCG 墨西哥 1931 与 BCG 丹麦菌株共享 62%的蛋白质斑点,与 BCG 菲普斯菌株共享 61%,与 BCG 东京菌株仅共享 48%。使用活动性结核病感染和结核菌素皮肤试验阳性的受试者的血清在 BCG 墨西哥 1931 中检测到 39 个反应性斑点。

结论

BCG 墨西哥 1931 的基因组小于 BCG 巴斯德和 BCG 东京菌株。描述了 BCG 墨西哥 1931 中的两个特定缺失(RDMex02 和 RDMex03)。RDMex02(fadD23)的缺失与增强的巨噬细胞结合有关,而 RDMex03 包含可能参与调节途径的基因。我们还首次描述了新的抗原蛋白。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1b9/3199284/b56ea58c35e0/1471-2164-12-493-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1b9/3199284/67723ef7d0a3/1471-2164-12-493-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1b9/3199284/79bbba748234/1471-2164-12-493-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1b9/3199284/ed173840bc72/1471-2164-12-493-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1b9/3199284/e062968b3b44/1471-2164-12-493-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1b9/3199284/b56ea58c35e0/1471-2164-12-493-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1b9/3199284/67723ef7d0a3/1471-2164-12-493-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1b9/3199284/79bbba748234/1471-2164-12-493-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1b9/3199284/ed173840bc72/1471-2164-12-493-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1b9/3199284/e062968b3b44/1471-2164-12-493-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1b9/3199284/b56ea58c35e0/1471-2164-12-493-5.jpg

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