伤寒沙门氏菌 Vi 胶囊位点的遗传异质性:斐济群体基因组研究

IF 4 2区 生物学 Q1 GENETICS & HEREDITY
Aneley Getahun Strobel, Andrew J. Hayes, Wytamma Wirth, Mikaele Mua, Tiko Saumalua, Orisi Cabenatabua, Vika Soqo, Varanisese Rosa, Nancy Wang, Jake A. Lacey, Dianna Hocking, Mary Valcanis, Adam Jenney, Benjamin P. Howden, Sebastian Duchene, Kim Mulholland, Richard A. Strugnell and Mark R. Davies
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引用次数: 0

摘要

伤寒是世界许多地方的地方病,在包括斐济在内的热带和亚热带发展中国家仍然是一个主要的公共卫生问题。为应对伤寒的高发病率,斐济北部省于 2023 年实施了伤寒结合疫苗(Vi-多糖结合破伤风类毒素)的大规模接种,作为一项公共卫生控制措施。在本研究中,我们确定了在全岛接种疫苗之前北部分区伤寒沙门氏菌的基因组流行病学,对斐济北部分区和中部分区2017–2019年期间发生的病例总数的85%(n=419)进行了测序。我们发现,在斐济流行的伤寒杆菌基因型 4.2 中,tviD 和 tviE 基因(负责 Vi-polysaccharide 合成)的核苷酸多态性相对于核心基因组水平较高。将这些发现扩展到具有全球代表性的 12 382 S. Typhi(86 个基因型集群)数据库中,显示出相同的 tviE 突变在整个 S. Typhi 群体中趋同进化的证据,表明 tvi 的选择是独立和全球性的。tvi 突变对 Vi 胶囊结构和其他表型特征的功能影响尚未完全阐明,但当与预测的 TviE 蛋白结构重叠时,常见的 tviE 多态性定位在预测的活性位点残基附近。鉴于 Vi- 多糖在伤寒杆菌生物学和疫苗接种中的核心作用,需要进一步综合流行病学、基因组和表型监测,以确定这些突变的传播和功能影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Genetic heterogeneity in the Salmonella Typhi Vi capsule locus: a population genomic study from Fiji
Typhoid fever is endemic in many parts of the world and remains a major public health concern in tropical and sub-tropical developing nations, including Fiji. To address high rates of typhoid fever, the Northern Division of Fiji implemented a mass vaccination with typhoid conjugate vaccine (Vi-polysaccharide conjugated to tetanus toxoid) as a public health control measure in 2023. In this study we define the genomic epidemiology of Salmonella Typhi in the Northern Division prior to island-wide vaccination, sequencing 85% (n=419) of the total cases from the Northern and Central Divisions of Fiji that occurred in the period 2017–2019. We found elevated rates of nucleotide polymorphisms in the tviD and tviE genes (responsible for Vi-polysaccharide synthesis) relative to core genome levels within the Fiji endemic S. Typhi genotype 4.2. Expansion of these findings within a globally representative database of 12 382 S. Typhi (86 genotyphi clusters) showed evidence of convergent evolution of the same tviE mutations across the S. Typhi population, indicating that tvi selection has occurred both independently and globally. The functional impact of tvi mutations on the Vi-capsular structure and other phenotypic characteristics are not fully elucidated, yet commonly occurring tviE polymorphisms localize adjacent to predicted active site residues when overlayed against the predicted TviE protein structure. Given the central role of the Vi-polysaccharide in S. Typhi biology and vaccination, further integrated epidemiological, genomic and phenotypic surveillance is required to determine the spread and functional implications of these mutations.
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来源期刊
Microbial Genomics
Microbial Genomics Medicine-Epidemiology
CiteScore
6.60
自引率
2.60%
发文量
153
审稿时长
12 weeks
期刊介绍: Microbial Genomics (MGen) is a fully open access, mandatory open data and peer-reviewed journal publishing high-profile original research on archaea, bacteria, microbial eukaryotes and viruses.
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