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侵袭性 emm28 型酿脓链球菌的遗传进化及其与芬兰年轻女性产褥期感染的显著相关性。

Genetic evolution of invasive emm28 Streptococcus pyogenes strains and significant association with puerperal infections in young women in Finland.

机构信息

Institute of Biomedicine, University of Turku, Turku, Finland.

Center for Molecular and Translational Human Infectious Diseases Research, Department of Pathology and Genomic Medicine, Houston Methodist Research Institute and Houston Methodist Hospital, Houston, TX, USA.

出版信息

Clin Microbiol Infect. 2021 Mar;27(3):420-427. doi: 10.1016/j.cmi.2020.04.004. Epub 2020 Apr 11.

DOI:10.1016/j.cmi.2020.04.004
PMID:32289480
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7780161/
Abstract

OBJECTIVES

Streptococcus pyogenes or group A streptococcus (GAS) is a human specific pathogen that annually infects over 700 million individuals. GAS strains of type emm28 are an abundant cause of invasive infections in Europe and North America.

METHODS

We conducted a population-based study on bacteraemic emm28 GAS cases in Finland, from 1995 to 2015. Whole-genome sequencing (WGS) was used to genetically characterize the bacterial isolates. Bayesian analysis of the population structure was used to define genetic clades. Register-linkage analysis was performed to test for association of emm28 GAS with delivery- or postpartum-related infections. A genome-wide association study was used to search for DNA sequences associated with delivery or puerperal infections.

RESULTS

Among 3060 bacteraemic cases reported during the study period, 714 were caused by emm28. Women comprised a majority of cases (59 %, 422/714), and were significantly over-represented (84.4 %, 162/192, p < 0.0001) among cases in the childbearing age group (20-40 years). Register-linkage analysis revealed strong association (p < 0.0001) of emm28 bacteraemias with delivery and puerperium. In this register-linkage analysis, 120 women with GAS bacteraemia were identified and linked to delivery, infections during delivery or puerperium time. Among these the proportion of cases caused by emm28 was significantly higher than any other emm type (55.8%, 67/120, p < 0.0001). Among the four genetic subclades identified, SC1B has dominated among the bacteraemic cases since 2000. Altogether 620 of 653 (94.9%) isolates belonged to SC1B. No specific sequence or genetic clade was found nonrandomly associated with delivery or puerperal infections.

CONCLUSIONS

Women of childbearing age were significantly overrepresented among bacteraemic emm28 GAS cases, and in particular were strongly associated with delivery and puerperium cases over the 21 years studied. The molecular mechanisms behind these associations are unclear and warrant further investigation.

摘要

目的

酿脓链球菌(Group A Streptococcus,GAS)又称化脓性链球菌,是一种仅感染人类的病原体,每年感染超过 7 亿人。emm28 型 GAS 菌株是欧洲和北美的主要侵袭性感染病原体。

方法

我们在芬兰开展了一项基于人群的emm28 型 GAS 菌血症病例研究,研究时间为 1995 年至 2015 年。采用全基因组测序(Whole-genome sequencing,WGS)对细菌分离株进行基因特征分析。贝叶斯种群结构分析用于定义遗传分支。登记链接分析用于检测 emm28 GAS 与分娩或产后相关感染之间的关联。全基因组关联研究用于搜索与分娩或产褥期感染相关的 DNA 序列。

结果

在研究期间报告的 3060 例菌血症病例中,714 例由 emm28 引起。女性占大多数(59%,422/714),在生育年龄组(20-40 岁)的病例中,女性的比例显著偏高(84.4%,162/192,p<0.0001)。登记链接分析显示,emm28 菌血症与分娩和产褥期密切相关(p<0.0001)。在该登记链接分析中,我们确定了 120 名患有 GAS 菌血症的女性,并与分娩、分娩期间或产褥期感染相关联。在这些病例中,由 emm28 引起的病例比例明显高于任何其他 emm 型(55.8%,67/120,p<0.0001)。在所确定的四个遗传亚群中,SC1B 自 2000 年以来一直主导菌血症病例。共有 653 株分离株中的 620 株(94.9%)属于 SC1B。未发现任何特定的序列或遗传分支与分娩或产褥期感染存在非随机关联。

结论

生育年龄的女性在酿脓链球菌 emm28 菌血症病例中所占比例显著偏高,在研究的 21 年间,与分娩和产褥期病例的关联尤为显著。这些关联背后的分子机制尚不清楚,值得进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc48/7780161/dd65efe75644/nihms-1650118-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc48/7780161/f98a5eadf7ff/nihms-1650118-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc48/7780161/65bac81707d4/nihms-1650118-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc48/7780161/dd65efe75644/nihms-1650118-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc48/7780161/f98a5eadf7ff/nihms-1650118-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc48/7780161/65bac81707d4/nihms-1650118-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc48/7780161/dd65efe75644/nihms-1650118-f0003.jpg

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