Data_Sheet_5_Phylogenetic Structure and Comparative Genomics of Multi-National Invasive Haemophilus influenzae Serotype a Isolates.DOCX

Recent reports have indicated a rise of invasive disease caused by Haemophilus influenzae serotype a (Hia) in North America and some European countries. The whole-genome sequences for a total of 410 invasive Hia isolates were obtained from 12 countries spanning the years of 1998 to 2019 and underwent phylogenetic and comparative genomic analysis in order to characterize the major strains causing disease and the genetic variation present among factors contributing to virulence and antimicrobial resistance. Among 410 isolate sequences received, 408 passed our quality control and underwent genomic analysis. Phylogenetic analysis revealed that the Hia isolates formed four genetically distinct clades: clade 1 (n = 336), clade 2 (n = 13), clade 3 (n = 3) and clade 4 (n = 56). A low diversity subclade 1.1 was found in clade 1 and contained almost exclusively North American isolates. The predominant sequence types in the Hia collection were ST-56 (n = 125), ST-23 (n = 98) and ST-576 (n = 51), which belonged to clade 1, and ST-62 (n = 54), which belonged to clade 4. Clades 1 and 4 contained predominantly North American isolates, and clades 2 and 3 predominantly contained European isolates. Evidence of the presence of capsule duplication was detected in clade 1 and 2 isolates. Seven of the virulence genes involved in endotoxin biosynthesis were absent from all Hia isolates. In general, the presence of known factors contributing to β-lactam antibiotic resistance was low among Hia isolates. Further tests for virulence and antibiotic susceptibility would be required to determine the impact of these variations among the isolates.

近期研究报道显示，北美及部分欧洲国家由a型流感嗜血杆菌（Haemophilus influenzae serotype a，Hia）引发的侵袭性疾病病例呈上升趋势。本数据集共纳入来自12个国家、1998年至2019年间采集的410株侵袭性Hia分离株的全基因组序列，通过系统发育与比较基因组学分析，对致病优势菌株以及毒力、抗菌耐药相关因子的遗传变异特征进行解析。
在所提交的410株分离株序列中，共408株通过质量控制并进入后续基因组分析。系统发育分析结果显示，Hia分离株可划分为4个遗传上独立的进化枝（clade）：进化枝1（n=336）、进化枝2（n=13）、进化枝3（n=3）与进化枝4（n=56）。
在进化枝1中发现一个低多样性亚进化枝（subclade）1.1，该亚进化枝几乎仅包含北美来源的分离株。本数据集收录的Hia分离株中，优势序列型（Sequence Type，ST）分别为ST-56（n=125）、ST-23（n=98）与ST-576（n=51），均属于进化枝1；另有ST-62（n=54）属于进化枝4。进化枝1与进化枝4的分离株以北美来源为主，进化枝2与进化枝3则以欧洲来源为主。
在进化枝1与进化枝2的分离株中，检测到荚膜重复的遗传特征。所有Hia分离株均缺失7种参与内毒素生物合成的毒力基因。总体而言，Hia分离株中已知的β-内酰胺类抗生素耐药相关因子携带率较低。后续需开展毒力与抗菌药敏试验，以明确上述遗传变异对各分离株的影响。