Data_Sheet_4_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.

近期研究报告显示，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，并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特征，以及毒力与抗菌耐药相关因子的遗传变异情况。在获取的410株分离株序列中，有408株通过质量控制并进入基因组学分析流程。系统发育分析结果显示，Hia分离株可划分为4个遗传特征迥异的进化枝：进化枝1（n=336）、进化枝2（n=13）、进化枝3（n=3）及进化枝4（n=56）。进化枝1中存在一个低多样性亚进化枝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）为属于进化枝1的ST-56（n=125）、ST-23（n=98）与ST-576（n=51），以及属于进化枝4的ST-62（n=54）。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则以欧洲来源的分离株居多。在进化枝1与进化枝2的分离株中，检测到荚膜复制的相关特征。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分离株中携带已知β-内酰胺类抗菌耐药相关因子的比例较低。需开展进一步的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。