应用全基因组测序技术分析侵袭性 B 群链球菌候选疫苗靶标、毒力因子和耐药特征的分布：一项多中心、基于人群的监测研究。

Distributions of candidate vaccine Targets, virulence Factors, and resistance features of invasive group B Streptococcus using Whole-Genome Sequencing: A Multicenter, population-based surveillance study.

机构信息

Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmacy, Center for Drug Safety and Policy Research, Xi'an Jiaotong University, Xi'an, Shaanxi, China.

National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.

出版信息

Vaccine. 2024 Jun 11;42(16):3564-3571. doi: 10.1016/j.vaccine.2024.04.062. Epub 2024 Apr 30.

DOI:10.1016/j.vaccine.2024.04.062

PMID:38692955

Abstract

BACKGROUND

Group B Streptococcus (GBS) is a leading cause of morbidity and mortality in young infants worldwide. This study aimed to investigate candidate GBS vaccine targets, virulence factors, and antimicrobial resistance determinants.

METHODS

We used whole-genome sequencing to characterize invasive GBS isolates from infants < 3 months of age obtained from a multicenter population-based study conducted from 2015 to 2021 in China.

RESULTS

Overall, seven serotypes were detected from 278 GBS isolates, four (Ia, Ib, III, V) of which accounted for 97.8 %. We detected 30 sequence types (including 10 novel types) that were grouped into six clonal complexes (CCs: CC1, CC10, CC17, CC19, CC23 and CC651); three novel ST groups in CC17 were detected, and the rate of CC17, considered a hyperinvasive neonatal clone complex, was attached to 40.6 % (113/278). A total of 98.9 % (275/278) of isolates harbored at least one alpha-like protein gene. All GBS isolates contained at least one of three pilus backbone determinants and the pilus types PI-2b and PI-1 + PI-2a accounted for 79.8 % of the isolates. The 112 serotype III/CC17 GBS isolates were all positive for hvgA. Most of the isolates (75.2 %) were positive for serine-rich repeat glycoprotein determinants (srr1or srr2). Almost all isolates possessed cfb (99.6 %), c1IE (100 %), lmb (95.3 %) or pavA (100 %) gene. Seventy-seven percent of isolates harboured more than three antimicrobial resistance genes with 28.4 % (79/278) gyrA quinoloneresistancedeterminants mutation, 83.8 % (233/278) carrying tet cluster genes and 77.3 % (215/278) carrying erm genes which mediated fluoroquinolone, tetracycline and clindamycin resistance, respectively."

CONCLUSIONS

The findings from this large whole-genome sequence of GBS isolates establish important baseline data required for further surveillance and evaluating the impact of future vaccine candidates.

摘要

背景

B 群链球菌（GBS）是全球导致婴幼儿发病和死亡的主要原因。本研究旨在研究 GBS 候选疫苗靶标、毒力因子和抗菌药物耐药决定因素。

方法

我们使用全基因组测序对 2015 年至 2021 年在中国进行的一项多中心基于人群的研究中获得的 <3 个月龄婴儿侵袭性 GBS 分离株进行了特征描述。

结果

总体而言，从 278 株 GBS 分离株中检测到 7 种血清型，其中 4 种（Ia、Ib、III、V）占 97.8%。我们检测到 30 种序列类型（包括 10 种新类型），分为 6 个克隆群（CC：CC1、CC10、CC17、CC19、CC23 和 CC651）；在 CC17 中检测到 3 种新型 ST 群，被认为是一种超侵袭性新生儿克隆群的 CC17 发生率为 40.6%（113/278）。278 株分离株中共有 98.9%（275/278）携带至少一种α样蛋白基因。所有 GBS 分离株均含有至少一种三种菌毛骨干决定簇之一，菌毛类型 PI-2b 和 PI-1+PI-2a 占分离株的 79.8%。112 株血清型 III/CC17 GBS 分离株均为 hvgA 阳性。大多数分离株（75.2%）为丝氨酸丰富重复糖蛋白决定簇（srr1 或 srr2）阳性。几乎所有分离株均含有 cfb（99.6%）、c1IE（100%）、lmb（95.3%）或 pavA（100%）基因。77%的分离株携带超过三种抗菌药物耐药基因，其中 28.4%（79/278）gyrA 喹诺酮耐药决定簇突变，83.8%（233/278）携带 tet 簇基因，77.3%（215/278）携带 erm 基因，分别介导氟喹诺酮类、四环素类和克林霉素耐药。