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新生儿败血症 B 群链球菌的基因组分析揭示了产时抗生素预防后克隆 CC17 的扩展以及与毒力和耐药性相关的特征。

Genomic Analysis of Group B Streptococcus from Neonatal Sepsis Reveals Clonal CC17 Expansion and Virulence- and Resistance-Associated Traits After Intrapartum Antibiotic Prophylaxis.

机构信息

State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.

Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center at Shanghai, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai, China.

出版信息

Clin Infect Dis. 2022 Dec 19;75(12):2153-2160. doi: 10.1093/cid/ciac331.

DOI:10.1093/cid/ciac331
PMID:35486954
Abstract

BACKGROUND

Group B Streptococcus (GBS) is a leading cause of invasive neonatal infections. This study aimed to investigate the trend of GBS serotype and genotype change and their correlation with antimicrobial resistance before and after implementation of intrapartum antibiotic prophylaxis (IAP).

METHODS

We performed serotyping, whole-genome sequencing, antimicrobial susceptibility testing, and single-nucleotide polymorphism (SNP)-based phylogenetic analysis on 238 invasive GBS isolates collected from October 1998 to February 2020 in Taiwan.

RESULTS

There were 7 serotypes and 6 clonal complexes (CCs) among the 238 GBS isolates, and more than half of the isolates carried multiple antimicrobial resistance genes. The expansion of CC17 strains and the increase in late-onset disease occurred synchronously after the implementation of IAP. Analysis of the carriage isolates from pregnant women showed diverse serotype distribution in the IAP era. The antimicrobial susceptibility testing showed that all 238 strains were susceptible to ampicillin and penicillin, while the number of various resistance genes in GBS genomes was found increased with the expansion of CC17. Compared with reference genomes, 697 nonsynonymous SNPs in 443 protein-coding genes were CC17 specific.

CONCLUSIONS

The study revealed the expansion of GBS CC17 and the increase of late-onset disease that occurred simultaneously with the implementation of IAP. Although the susceptibility of CC17 to antimicrobial agents is not different from that of other sequence types at present, GBS with phenotypic resistance to antimicrobials may emerge in the future, given the environmental selection pressure and the continued accumulation of SNP mutations.

摘要

背景

B 群链球菌(GBS)是导致新生儿侵袭性感染的主要原因。本研究旨在调查实施产时抗生素预防(IAP)前后 GBS 血清型和基因型变化及其与抗菌药物耐药性的相关性。

方法

我们对 1998 年 10 月至 2020 年 2 月在台湾收集的 238 株侵袭性 GBS 分离株进行了血清分型、全基因组测序、抗菌药物敏感性试验和基于单核苷酸多态性(SNP)的系统发育分析。

结果

238 株 GBS 分离株中有 7 种血清型和 6 种克隆群(CC),超过一半的分离株携带多种抗菌药物耐药基因。IAP 实施后,CC17 菌株的扩张和晚发型疾病的增加同时发生。对孕妇携带分离株的分析显示,IAP 时代血清型分布多样。抗菌药物敏感性试验表明,所有 238 株均对氨苄西林和青霉素敏感,而 GBS 基因组中各种耐药基因的数量随着 CC17 的扩张而增加。与参考基因组相比,443 个蛋白编码基因中有 697 个非同义 SNP 是 CC17 特有的。

结论

本研究揭示了 GBS CC17 的扩张和晚发型疾病的增加,这与 IAP 的实施同时发生。虽然 CC17 对抗菌药物的敏感性与其他序列类型目前没有区别,但鉴于环境选择压力和 SNP 突变的持续积累,具有表型耐药性的 GBS 可能会出现。

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