Genomic and phylogenetic analysis of Salmonella Typhimurium and its monophasic variants responsible for invasive endemic infections in Colombia
Genomic and phylogenetic analysis of Salmonella Typhimurium and its monophasic variants responsible for invasive endemic infections in Colombia
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DOI：
10.1101/588608
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发表时间：
2019-03
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通讯作者：
Yan Li;Caisey V. Pulford;P. Díaz;B. Perez-Sepulveda;C. Duarte;A. Predeus;Magdalena Wiesner;D. Heavens;Ross Low;Christian Schudoma;J. Lipscombe;A. Montaño;N. Hall;J. Moreno;J. Hinton
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作者：
Yan Li;Caisey V. Pulford;P. Díaz;B. Perez-Sepulveda;C. Duarte;A. Predeus;Magdalena Wiesner;D. Heavens;Ross Low;Christian Schudoma;J. Lipscombe;A. Montaño;N. Hall;J. Moreno;J. Hinton
沙门氏菌病是一种地方性人类感染，与哥伦比亚各地的散发病例和暴发有关。鼠伤寒是哥伦比亚最常见的肠道沙门氏菌血清型，占沙门氏菌感染的32.5%。全基因组测序（WGS）在欧洲和美国越来越多地用于研究沙门氏菌的流行病学，但在哥伦比亚，尚未有基于WGS的与血流感染相关的沙门氏菌分析。在这里，我们分析了209个哥伦比亚S。鼠伤寒沙门氏菌和嗜水气单胞菌。4，[5]，12：i：-1999年至2017年来自哥伦比亚的分离株。我们使用基于核心基因组的最大似然树来定义七个不同的簇，这些簇主要是序列类型（ST）19分离株。我们还确定了在哥伦比亚报告的第一个ST 313和单相ST 34分离株。用贝叶斯树重建每个聚类的历史，以揭示进化的时间轴。聚类7与欧洲多药耐药（MDR）DT 104密切相关。2016年，第4簇成为沙门氏菌的主要变种，对萘啶酸的耐药性与质粒编码的qnrB 19基因有关。我们的研究结果表明，多个转移的S。欧洲和哥伦比亚之间的鼠伤寒。鼠伤寒沙门氏菌和双相沙门氏菌4，[5]，12：i：-的大规模基因组测序涉及哥伦比亚的血流分离株。在过去的20年里，这两种血清型造成了哥伦比亚约1/3的沙门氏菌感染。为了确定种群结构，我们使用全基因组测序，进行计算机序列分型，获得系统发育树，推断进化历史，检测质粒和原噬菌体，并将抗生素耐药（AMR）基因型与表型相关联。不同的集群显示时间的替代。哥伦比亚序列类型313与非洲血统不同，因为缺乏关键的毒力相关基因bstA。根据进化史和AMR谱，哥伦比亚的一个集群可能属于DT 104的全球流行。近年来最常见的簇是耐萘啶酸，并携带质粒介导的抗生素耐药基因qnrB 19。我们的研究结果将为哥伦比亚公共卫生部门正在进行的抗击沙门氏菌病的努力提供信息。
Salmonellosis is an endemic human infection, associated with both sporadic cases and outbreaks throughout Colombia. Typhimurium is the most common Colombian serovar of Salmonella enterica, responsible for 32.5% of the Salmonella infections. Whole genome sequencing (WGS) is being used increasingly in Europe and the USA to study the epidemiology of Salmonella, but there has not yet been a WGS-based analysis of Salmonella associated with bloodstream infection in Colombia. Here, we analysed 209 genome sequences of Colombian S. Typhimurium and monophasic S. 4,[5],12:i:-isolates from Colombia from 1999 to 2017. We used a core genome-based maximum likelihood tree to define seven distinct clusters which were predominantly Sequence Type (ST) 19 isolates. We also identified the first ST313 and monophasic ST34 isolates to be reported in Colombia. The history of each cluster was reconstructed with a Bayesian tree to reveal a timeline of evolution. Cluster 7 was closely related to European multidrug-resistant (MDR) DT104. Cluster 4 became the dominant variant of Salmonella in 2016, and resistance to nalidixic acid was associated with a plasmid-encoded qnrB19 gene. Our findings suggest multiple transfers of S. Typhimurium between Europe and Colombia. Author summary The large-scale genome sequencing of Salmonella Typhimurium and monophasic Salmonella 4,[5],12:i:-involved bloodstream isolates from Colombia. The two serovars were responsible for about 1/3 of Salmonella infections in Colombia in the past 20 years. To identify the population structure we used Whole Genome Sequencing, performed in silico sequence typing, obtained phylogenetic trees, inferred the evolutionary history, detected the plasmids and prophages, and associated the antibiotic resistance (AMR) genotype with phenotype. Different clusters showed temporal replacement. The Colombian sequence type 313 was distinct from African lineages due to the absence of a key virulence-related gene, bstA. One of the Colombian clusters is likely to belong to the global epidemic of DT104, according to the evolutionary history and the AMR profile. The most common cluster in recent years was resistant to nalidixic acid and carried a plasmid-mediated antibiotic resistant gene qnrB19. Our findings will inform the ongoing efforts to combat Salmonellosis by Colombian public health departments.