Data Sheet 1_Multiple Brucella melitensis lineages are driving the human brucellosis epidemic in Shaanxi Province, China: evidence from whole genome sequencing-based analysis.pdf

IntroductionHuman brucellosis is a severe public concern in Shaanxi Province, China, and investigating the epidemiological relationship and transmission pattern of B. melitensis is necessary to devise control strategies.
MethodsIn this study, a conventional bio-typing approach and whole genome sequencing of single-nucleotide polymorphisms (SNPs) were employed to identify 189 strains.
ResultsBased on the conventional bio-typing, 189 Brucella strains were identified as B. melitensis, of which 14 were in bv. 1, 145 were in bv. 3, and 30 were variant, and the Brucella strains were distributed in all ten cities in Shaanxi Province. SNP analysis was used to identify genetic variation in 189 B. melitensis genomes, and maximum-likelihood was used to generate a phylogeny that identified two clades (A and B) and 19 sequence types (STs). The two clades were highly diverse and exclusively of Eastern Mediterranean origin. Clade B contained 18 STs (2-19), with most isolates originating from a broad swath, implying that multiple B. melitensis lineages circulated in Shaanxi. The 19 STs were composed of 3 to 46 strains isolated from different counties and years, suggesting that multiple cross-county brucellosis outbreak events are driven by multiple B. melitensis lineages. Global phylogenetic analysis revealed that clade A was close to GTIIb, and clade B was placed in the GTIIh lineage, expanding the known diversity of B. melitensis from China.
ConclusionThe human brucellosis epidemic in Shaanxi is driven by multiple indigenous circulating B. melitensis lineages, the knowledge of which will contribute to devising a control strategy and providing the foundation for a comprehensive regional phylogeny of this important zoonotic pathogen.

引言 布鲁氏菌病（human brucellosis）在中国陕西省是严重的公共卫生关切问题，为制定科学的防控策略，开展羊种布鲁氏菌（Brucella melitensis, B. melitensis）的流行病学关联与传播模式研究十分必要。
方法 本研究采用传统生物分型方法与全基因组单核苷酸多态性（single-nucleotide polymorphisms, SNPs）测序技术，对189株菌株进行鉴定。
结果 基于传统生物分型，189株布鲁氏菌均被鉴定为羊种布鲁氏菌，其中14株为生物型1（bv.1）、145株为生物型3（bv.3），30株为变异株，且所有菌株均分布于陕西省全部10个地市。通过SNP分析解析189株羊种布鲁氏菌基因组的遗传变异特征，并采用最大似然法构建系统发育树，共鉴定出2个进化分支（A分支与B分支）以及19种序列型（sequence types, STs）。两个进化分支具有高度遗传多样性，且均起源于东地中海地区。B分支包含18种序列型（2至19号），多数分离株来自广泛地理区域，提示陕西省境内存在多种羊种布鲁氏菌谱系流行。19种序列型分别对应3至46株分离自不同县域与不同年份的菌株，表明陕西省多起跨县域布鲁氏菌病暴发事件均由多种羊种布鲁氏菌谱系驱动。全球系统发育分析显示，A分支与GTIIb型亲缘关系相近，B分支则归属于GTIIh谱系，该发现拓展了中国境内羊种布鲁氏菌的已知遗传多样性范围。
结论 陕西省人间布鲁氏菌病的流行由多种本土流行的羊种布鲁氏菌谱系所驱动，本研究结果可为制定针对性防控策略提供理论支撑，并为该重要人兽共患病病原构建全面的区域系统发育图谱奠定基础。