Data_Sheet_3_Phylogenetic Structure and Comparative Genomics of Multi-National Invasive Haemophilus influenzae Serotype a Isolates.XLSX

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）引发的侵袭性疾病发病率呈上升趋势。本研究共获取了1998年至2019年间来自12个国家的410株侵袭性Hia分离株的全基因组序列，随后对其开展系统发育与比较基因组学分析，以明确致病优势菌株的特征，以及毒力与抗菌耐药相关因子所携带的遗传变异情况。在接收的410株分离株序列中，共有408株通过质量控制并进入基因组分析流程。系统发育分析结果显示，Hia分离株可分为4个遗传特征迥异的进化支：进化支1（n=336）、进化支2（n=13）、进化支3（n=3）及进化支4（n=56）。在进化支1中发现了一个低多样性亚进化支1.1，其分离株几乎全部来自北美地区。本数据集收录的Hia分离株中，优势序列型（Sequence Type, ST）为ST-56（n=125）、ST-23（n=98）及ST-576（n=51），均隶属于进化支1；另有ST-62（n=54）隶属于进化支4。进化支1与4的分离株以北美来源为主，而进化支2与3则以欧洲来源分离株占多数。在进化支1和2的分离株中检测到荚膜复制的相关证据。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分离株中携带已知β-内酰胺类抗生素耐药相关因子的比例较低。后续需开展毒力与抗生素敏感性检测，以明确上述遗传变异对各分离株的影响。