Nontypeable Haemophilus influenzae (NTHi) colonizes human upper respiratory airways and plays a key role in the course and pathogenesis of acute exacerbations of chronic obstructive pulmonary disease (COPD). Currently, it is not possible to distinguish COPD isolates of NTHi from other clinical isolates of NTHi using conventional genotyping methods. Here, we analysed the core and accessory genome of 568 NTHi isolates, including 40 newly sequenced isolates, to look for genetic distinctions between NTHi isolates from COPD with respect to other illnesses, including otitis media, meningitis and pneumonia. Phylogenies based on polymorphic sites in the core-genome did not show discrimination between NTHi strains collected from different clinical phenotypes. However, pan-genome-wide association studies identified 79 unique NTHi accessory genes that were significantly associated with COPD. Furthermore, many of the COPD-related NTHi genes have known or predicted roles in virulence, transmembrane transport of metal ions and nutrients, cellular respiration and maintenance of redox homeostasis. This indicates that specific genes may be required by NTHi for its survival or virulence in the COPD lung. These results advance our understanding of the pathogenesis of NTHi infection in COPD lungs.

中文翻译：

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全基因组分析揭示了与其他临床表型相比，来自慢性阻塞性肺疾病的不可分型流感嗜血杆菌分离株之间的基因含量差异。

不可分型流感嗜血杆菌 (NTHi) 定植于人类上呼吸道，并在慢性阻塞性肺疾病 (COPD) 急性加重的过程和发病机制中起关键作用。目前，不可能使用传统的基因分型方法将 COPD 分离株 NTHi 与其他 NTHi 临床分离株区分开来。在这里，我们分析了 568 个 NTHi 分离株的核心和辅助基因组，包括 40 个新测序的分离株，以寻找来自 COPD 的 NTHi 分离株与其他疾病（包括中耳炎、脑膜炎和肺炎）之间的遗传差异。基于核心基因组中多态位点的系统发育未显示从不同临床表型收集的 NTHi 菌株之间的区别。然而，全基因组关联研究确定了 79 个与 COPD 显着相关的独特 NTHi 辅助基因。此外，许多与 COPD 相关的 NTHi 基因在毒力、金属离子和营养物质的跨膜转运、细胞呼吸和氧化还原稳态的维持中具有已知或预测的作用。这表明 NTHi 可能需要特定基因才能在 COPD 肺中存活或发挥毒力。这些结果促进了我们对 COPD 肺部 NTHi 感染发病机制的理解。