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空肠弯曲菌毒力基因与免疫炎症生物标志物与巴西东北部儿童生长障碍的关系。

Campylobacter jejuni virulence genes and immune-inflammatory biomarkers association with growth impairment in children from Northeastern Brazil.

机构信息

Institute of Biomedicine for Brazilian Semiarid, Federal University of Ceará, Rua Coronel Nunes de Melo, 1315, Rodolfo Teófilo, Fortaleza, Ceará, 60430270, Brazil.

Institute for the Promotion of Nutrition and Human Development, 15 Professor Carlos Lobo, Fortaleza, Ceará, 60281-740, Brazil.

出版信息

Eur J Clin Microbiol Infect Dis. 2018 Oct;37(10):2011-2020. doi: 10.1007/s10096-018-3337-0. Epub 2018 Jul 26.

DOI:10.1007/s10096-018-3337-0
PMID:30051355
Abstract

Campylobacter spp. have been associated with anthropometric Z-score decrements, but the role of specific virulence genes associated with these outcomes has not been explored. This study aimed to investigate whether specific Campylobacter jejuni virulence-related gene and immune-inflammatory biomarkers are associated with malnutrition in children from Northeastern Brazil. A case-control study was performed in Fortaleza, Brazil. Children aging 6-24 months were characterized as malnourished (cases) if weight-for-age Z-score (WAZ) = 2 and as nourished (controls) if WAZ ≥ 1. DNA samples were extracted from stools and screened for C. jejuni/coli by real-time PCR. A subsequent C. jejuni-specific PCR was employed and positive samples were evaluated for 18 C. jejuni virulence genes by using four multiplex PCRs. C. jejuni was detected in 9.71% (33/340) of the children's samples, being 63.63% (21/33) from nourished and 37.37% (12/33) from malnourished children. The cadF, iamA, cheW, and sodB genes were the most frequent genes (100%, 90.9%, 87.9%, and 75.8%, respectively), while some others (ceuE, jlpA, pldA, and pVir) showed low rates (all below 6%). Malnourished children were significantly associated with infection with C. jejuni strains lacking cdtB gene (active subunit of cytolethal distending toxin) and harboring flgE gene (flagellar hook protein). These strains were also associated with children presenting increased serum SAA and sCD-14, but decreased IgG anti-LPS. These data reinforce the impact of Campylobacter jejuni infection on children without diarrhea and highlight the contribution of a specific virulence gene profile, cdtB(-)flgE(+) and increased systemic response in malnutrition children.

摘要

空肠弯曲菌与人体测量 Z 分数下降有关,但与这些结果相关的特定毒力基因的作用尚未得到探索。本研究旨在调查巴西东北部儿童中是否存在特定的空肠弯曲菌相关毒力基因和免疫炎症生物标志物与营养不良有关。本研究在巴西福塔雷萨进行了病例对照研究。6-24 月龄的儿童,如果体重与年龄 Z 分数(WAZ)≤2,则被定义为营养不良(病例),如果 WAZ≥1,则被定义为营养良好(对照)。从粪便中提取 DNA 样本,并通过实时 PCR 检测空肠弯曲菌/大肠埃希菌。随后进行空肠弯曲菌特异性 PCR,如果阳性,则采用 4 重多重 PCR 检测 18 种空肠弯曲菌毒力基因。在 340 名儿童样本中检测到空肠弯曲菌,其中 9.71%(33/340)来自营养良好的儿童,37.37%(12/33)来自营养不良的儿童。cadF、iamA、cheW 和 sodB 基因是最常见的基因(分别为 100%、90.9%、87.9%和 75.8%),而其他一些基因(ceuE、jlpA、pldA 和 pVir)的频率较低(均低于 6%)。缺乏 cdtB 基因(细胞毒素扩张毒素的活性亚基)和携带 flgE 基因(鞭毛钩蛋白)的空肠弯曲菌感染与营养不良儿童显著相关。这些菌株还与血清 SAA 和 sCD-14 增加、IgG 抗 LPS 减少的儿童有关。这些数据强调了空肠弯曲菌感染对无腹泻儿童的影响,并突出了特定毒力基因谱 cdtB(-)flgE(+)和全身性反应增加在营养不良儿童中的作用。

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