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对巴布亚新几内亚的伤寒沙门氏菌进行全基因组序列分析,揭示了对抗菌药物敏感的 2.1.7 基因型定型种群。

Whole genome sequence analysis of Salmonella Typhi in Papua New Guinea reveals an established population of genotype 2.1.7 sensitive to antimicrobials.

机构信息

London School of Hygiene & Tropical Medicine, London, United Kingdom.

Department of Infectious Diseases, Central Clinical School, Monash University, Melbourne, Australia.

出版信息

PLoS Negl Trop Dis. 2022 Mar 28;16(3):e0010306. doi: 10.1371/journal.pntd.0010306. eCollection 2022 Mar.

DOI:10.1371/journal.pntd.0010306
PMID:35344544
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8989336/
Abstract

BACKGROUND

Typhoid fever, a systemic infection caused by Salmonella enterica serovar Typhi, remains a considerable public health threat in impoverished regions within many low- and middle-income settings. However, we still lack a detailed understanding of the emergence, population structure, molecular mechanisms of antimicrobial resistance (AMR), and transmission dynamics of S. Typhi across many settings, particularly throughout the Asia-Pacific islands. Here we present a comprehensive whole genome sequence (WGS) based overview of S. Typhi populations circulating in Papua New Guinea (PNG) over 30 years.

PRINCIPLE FINDINGS

Bioinformatic analysis of 86 S. Typhi isolates collected between 1980-2010 demonstrated that the population structure of PNG is dominated by a single genotype (2.1.7) that appears to have emerged in the Indonesian archipelago in the mid-twentieth century with minimal evidence of inter-country transmission. Genotypic and phenotypic data demonstrated that the PNG S. Typhi population appears to be susceptible to former first line drugs for treating typhoid fever (chloramphenicol, ampicillin and co-trimoxazole), as well as fluoroquinolones, third generation cephalosporins, and macrolides. PNG genotype 2.1.7 was genetically conserved, with very few deletions, and no evidence of plasmid or prophage acquisition. Genetic variation among this population was attributed to either single point mutations, or homologous recombination adjacent to repetitive ribosomal RNA operons.

SIGNIFICANCE

Antimicrobials remain an effective option for the treatment of typhoid fever in PNG, along with other intervention strategies including improvements to water, sanitation and hygiene (WaSH) related infrastructure and potentially the introduction of Vi-conjugate vaccines. However, continued genomic surveillance is warranted to monitor for the emergence of AMR within local populations, or the introduction of AMR associated genotypes of S. Typhi in this setting.

摘要

背景

伤寒是由伤寒沙门氏菌血清型 Typhi 引起的全身性感染,在许多低收入和中等收入国家的贫困地区仍然是一个相当大的公共卫生威胁。然而,我们仍然缺乏对伤寒沙门氏菌在许多环境中的出现、种群结构、抗菌药物耐药性(AMR)的分子机制以及传播动态的详细了解,特别是在整个亚太岛屿地区。在这里,我们呈现了一个基于全基因组序列(WGS)的概述,介绍了 30 多年来在巴布亚新几内亚(PNG)流行的伤寒沙门氏菌种群。

主要发现

对 1980 年至 2010 年间收集的 86 株伤寒沙门氏菌的生物信息学分析表明,PNG 的种群结构主要由一种单一的基因型(2.1.7)主导,这种基因型似乎在 20 世纪中叶在印度尼西亚群岛出现,几乎没有证据表明存在国与国之间的传播。基因型和表型数据表明,PNG 的伤寒沙门氏菌种群似乎对治疗伤寒的前一线药物(氯霉素、氨苄西林和复方磺胺甲噁唑)以及氟喹诺酮类、第三代头孢菌素和大环内酯类药物敏感。PNG 基因型 2.1.7 在遗传上是保守的,只有很少的缺失,没有质粒或前噬菌体获得的证据。该人群中的遗传变异归因于单点突变,或与核糖体 RNA 操纵子相邻的同源重组。

意义

在 PNG,抗生素仍然是治疗伤寒的有效选择,同时还需要采取其他干预策略,包括改善与水、卫生和环境卫生(WaSH)相关的基础设施,以及可能引入 Vi 结合疫苗。然而,需要继续进行基因组监测,以监测当地人群中 AMR 的出现,或在该环境中引入与 AMR 相关的伤寒沙门氏菌基因型。

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