Leekitcharoenphon Pimlapas, Hendriksen Rene S, Le Hello Simon, Weill François-Xavier, Baggesen Dorte Lau, Jun Se-Ran, Ussery David W, Lund Ole, Crook Derrick W, Wilson Daniel J, Aarestrup Frank M
Research Group for Genomic Epidemiology, National Food Institute, Technical University of Denmark, Kgs. Lyngby, Denmark Center for Biological Sequence Analysis, Department of System Biology, Technical University of Denmark, Kgs. Lyngby, Denmark
Research Group for Genomic Epidemiology, National Food Institute, Technical University of Denmark, Kgs. Lyngby, Denmark.
Appl Environ Microbiol. 2016 Apr 4;82(8):2516-26. doi: 10.1128/AEM.03821-15. Print 2016 Apr.
It has been 30 years since the initial emergence and subsequent rapid global spread of multidrug-resistant Salmonella entericaserovar Typhimurium DT104 (MDR DT104). Nonetheless, its origin and transmission route have never been revealed. We used whole-genome sequencing (WGS) and temporally structured sequence analysis within a Bayesian framework to reconstruct temporal and spatial phylogenetic trees and estimate the rates of mutation and divergence times of 315S Typhimurium DT104 isolates sampled from 1969 to 2012 from 21 countries on six continents. DT104 was estimated to have emerged initially as antimicrobial susceptible in ∼1948 (95% credible interval [CI], 1934 to 1962) and later became MDR DT104 in ∼1972 (95% CI, 1972 to 1988) through horizontal transfer of the 13-kb Salmonella genomic island 1 (SGI1) MDR region into susceptible strains already containing SGI1. This was followed by multiple transmission events, initially from central Europe and later between several European countries. An independent transmission to the United States and another to Japan occurred, and from there MDR DT104 was probably transmitted to Taiwan and Canada. An independent acquisition of resistance genes took place in Thailand in ∼1975 (95% CI, 1975 to 1990). In Denmark, WGS analysis provided evidence for transmission of the organism between herds of animals. Interestingly, the demographic history of Danish MDR DT104 provided evidence for the success of the program to eradicate Salmonellafrom pig herds in Denmark from 1996 to 2000. The results from this study refute several hypotheses on the evolution of DT104 and suggest that WGS may be useful in monitoring emerging clones and devising strategies for prevention of Salmonella infections.
多重耐药性肠炎沙门氏菌鼠伤寒血清型DT104（MDR DT104）首次出现并随后在全球迅速传播至今已有30年。然而，其起源和传播途径从未被揭示。我们使用全基因组测序（WGS）以及在贝叶斯框架内进行的时间结构化序列分析，来重建时间和空间系统发育树，并估计从1969年至2012年从六大洲21个国家采集的315株鼠伤寒血清型DT104分离株的突变率和分化时间。据估计，DT104最初于1948年左右作为抗菌药物敏感型出现（95%可信区间[CI]，1934年至1962年），后来在1972年左右通过将13 kb的沙门氏菌基因组岛1（SGI1）多药耐药区域水平转移到已含有SGI1的敏感菌株中，变成了MDR DT104。随后发生了多次传播事件，最初从中欧开始，后来在几个欧洲国家之间传播。发生了一次独立传播到美国以及另一次传播到日本的情况，MDR DT104可能从那里传播到了台湾和加拿大。1975年左右（95% CI，1975年至1990年）在泰国发生了一次独立的耐药基因获得事件。在丹麦，WGS分析为该生物体在动物群体之间的传播提供了证据。有趣的是，丹麦MDR DT104的种群历史为1996年至2000年丹麦从猪群中根除沙门氏菌的计划的成功提供了证据。这项研究的结果驳斥了关于DT104进化的几个假设，并表明WGS可能有助于监测新出现的克隆体以及制定预防沙门氏菌感染的策略。
