Accessory Genome Dynamics and Structural Variation of Shigella from Persistent Infections.
Accessory Genome Dynamics and Structural Variation of Shigella from Persistent Infections.
复制标题
持续感染志贺氏菌的副基因组动态及结构变异
DOI：
10.1128/mbio.00254-21
复制
发表时间：
2021-04-27
期刊：
影响因子：
6.4
通讯作者：
Baker KS
中科院分区：
文献类型：
--
作者：
Bengtsson RJ;Dallman TJ;Allen H;De Silva PM;Stenhouse G;Pulford CV;Bennett RJ;Jenkins C;Baker KS
志贺氏菌属是革兰氏阴性菌，是志贺氏菌病的病原，志贺氏菌病是低收入国家五岁以下儿童腹泻病的第二大常见病因。在高收入国家，志贺氏菌病也是男男性行为者中的一种性传播疾病。志贺氏菌病是一种主要由福氏志贺氏菌和索内志贺氏菌引起的腹泻疾病。感染被认为在很大程度上是自限性的，在清除后提供中短期和血清型特异性免疫。然而，已经报告了男男性行为（MSM）相关志贺氏菌病病例，其中可能由于持续携带或再次感染同一血清型，在间隔1至1862天的个体中连续取样相同血清型的志贺氏菌。在这里，我们研究了msm相关的flexneri和sonnei分离株的辅助基因组动力学，这些分离株在不同的时间间隔从个体患者中连续取样，以阐明这些重要病原体在感染过程中的适应性。我们发现可能与持续感染/携带相关且具有较小的单核苷酸多态性（SNP）距离的配对，显示出与可能与再感染相关且具有较大SNP距离的配对相比，附件基因组含量的变化明显更小。我们观察到志贺氏菌在运输过程中获得抗微生物药物耐药性，包括在运输过程中获得广谱β -内酰胺酶基因。最后，我们在7对（5对慢性和2对再感染相关的）来自男男性行为综合症相关流行亚谱系的flexneri 3a分离株中探索了大的染色体结构变异和重排，揭示了在插入序列元件介导的分离对中几个共同区域的变异，并构成了不同的预测功能谱。本研究提供了志贺氏菌在持续感染/携带期间附属基因组动态变化和大结构基因组变化的见解。此外，我们还创建了全球重要病原体S. flexneri 3a的完整参考基因组和生物银行分离物。
Shigella spp. are Gram-negative bacteria that are the etiological agent of shigellosis, the second most common cause of diarrheal illness among children under the age of five in low-income countries. In high-income countries, shigellosis is also a sexually transmissible disease among men who have sex with men. Shigellosis is a diarrheal disease caused mainly by Shigella flexneri and Shigella sonnei. Infection is thought to be largely self-limiting, with short- to medium-term and serotype-specific immunity provided following clearance. However, cases of men who have sex with men (MSM)-associated shigellosis have been reported where Shigella of the same serotype were serially sampled from individuals between 1 and 1,862 days apart, possibly due to persistent carriage or reinfection with the same serotype. Here, we investigate the accessory genome dynamics of MSM-associated S. flexneri and S. sonnei isolates serially sampled from individual patients at various days apart to shed light on the adaptation of these important pathogens during infection. We find that pairs likely associated with persistent infection/carriage and with a smaller single nucleotide polymorphism (SNP) distance, demonstrated significantly less variation in accessory genome content than pairs likely associated with reinfection, and with a greater SNP distance. We observed antimicrobial resistance acquisition during Shigella carriage, including the gain of an extended-spectrum beta-lactamase gene during carriage. Finally, we explored large chromosomal structural variations and rearrangements in seven (five chronic and two reinfection associated) pairs of S. flexneri 3a isolates from an MSM-associated epidemic sublineage, which revealed variations at several common regions across isolate pairs, mediated by insertion sequence elements and comprising a distinct predicted functional profile. This study provides insight on the variation of accessory genome dynamics and large structural genomic changes in Shigella during persistent infection/carriage. In addition, we have also created a complete reference genome and biobanked isolate of the globally important pathogen, S. flexneri 3a.
影响因子：
12.3
作者：
Koch A;Wilkinson RJ
通讯作者：
Wilkinson RJ